The Salmonella pathogenicity islands(SPIs) play crucial roles in the progression of Salmonella infection. In this study, we constructed an improved λ Red homologous recombination system to prepare single and triple d...The Salmonella pathogenicity islands(SPIs) play crucial roles in the progression of Salmonella infection. In this study, we constructed an improved λ Red homologous recombination system to prepare single and triple deletion mutants of 3 prominent SPIs(SPI-1, 2, and 3), aiming at the impact of deletion on morphology, carbon source metabolism, adhesion and invasion capacity, in vivo colonization, and immune efficacy in chicks. Our examination revealed that the surface of the single deletion mutants(SM6ΔSPI1, ΔSPI2, and ΔSPI3) exhibited a more rugged texture and appeared to be enveloped in a layer of transparent colloid, whereas the morphology of the triple deletion mutant(SM6ΔSPI1&2&3) remained unaltered when compared to the parent strain. The carbon metabolic spectrum of the SPI mutants underwent profound alterations, with a notable and statistically significant modification observed in 30 out of 95 carbon sources, primarily carbohydrates(17 out of 30). Furthermore, the adhesion capacity of the 4 mutants to Caco-2 cells was significantly reduced when compared to that of the parent strain. Moreover,the invasion capacity of mutants SM6ΔSPI1 and SM6ΔSPI1&2&3 exhibited a substantial decrease, while it was enhanced to varying degrees for SM6ΔSPI3 and SM6ΔSPI2. Importantly, none of the 4 mutants induced any clinical symptoms in the chicks. However, they did transiently colonize the spleen and liver. Notably, the SM6ΔSPI1&2&3mutant was rapidly cleared from both the spleen and liver within 8 days post-infection and no notable pathological changes were observed in the organs. Additionally, when challenged, the mutants immunized groups displayed a significant increase in antibody levels and alterations in the CD3+CD4+ and CD3+CD8+ subpopulations, and the levels of IL-4 and IFN-γ cytokines in the SM6ΔSPI1&2&3 immunized chicken serum surpassed those of other groups.In summary, the successful construction of the 4 SPI mutants lays the groundwork for further exploration into the pathogenic(including metabolic) mechanisms of SPIs and the development of safe and effective live attenuated Salmonella vaccines or carriers.展开更多
Dear Editor,The highly pathogenic avian influenza viruses(HPAIVs)are important epizootic and zoonotic pathogens that cause significant economic losses to the poultry industry and pose a serious risk to veterinary and ...Dear Editor,The highly pathogenic avian influenza viruses(HPAIVs)are important epizootic and zoonotic pathogens that cause significant economic losses to the poultry industry and pose a serious risk to veterinary and public health.Wild birds have been recognized as the primary reservoirs for influenza A virus,and some species show little sign of clinical disease or even can be asymptomatic during long distance carriers of the virus(Lycett et al.,2019).Since it was first discovered in 1959,the H5Nx HPAIVs have spread globally and cause outbreaks in wild birds,poultry and sporadic human and other mammalian infections(Lycett et al.,2019).Due to the reassortant events of diverse strains facilitated by migratory waterfowl,the clade 2.3.4.4 of H5Nx viruses acquiring neuraminidase(NA)gene from other low pathogenicity avian influenza viruses(LPAIVs)emerged in 2014 and gradually became the dominant sub-clade(Lee et al.,2017).展开更多
Respiratory infections are associated with high morbidity and mortality and are a major global health problem[1].Acute respiratory infections are caused by multiple respiratory pathogens,including viruses and bacteria...Respiratory infections are associated with high morbidity and mortality and are a major global health problem[1].Acute respiratory infections are caused by multiple respiratory pathogens,including viruses and bacteria.Viral-bacterial co-infections,which have become increasingly common and a global concern,can lead to substantial complications,causing higher morbidity and adverse prognosis[2].Previous studies have reported low positive detection rates of targeted pathogens related to acute respiratory infections,owing to the limited number of detected pathogens and variations in the sensitivity of diagnostic methods[3-4].Low positive detection rates may impede our understanding of respiratory pathogen characteristics and hamper the development of precise treatment and prevention strategies.展开更多
Reductive soil disinfestation(RSD)is commonly employed for soil remediation in greenhouse cultivation.However,its influence on antibiotic resistance genes(ARGs)in soil remains uncertain.This study investigated the dyn...Reductive soil disinfestation(RSD)is commonly employed for soil remediation in greenhouse cultivation.However,its influence on antibiotic resistance genes(ARGs)in soil remains uncertain.This study investigated the dynamic changes in soil communities,potential bacterial pathogens,and ARG profiles under various organicmaterial treatments during RSD,including distillers’grains,potato peel,peanut vine,and peanut vine combined with charcoal.Results revealed that applying diverse organic materials in RSD significantly altered bacterial community composition and diminished the relative abundance of potential bacterial pathogens(P<0.05).The relative abundance of high-risk ARGs decreased by 10.7%-30.6%after RSD treatments,the main decreased ARG subtypeswere AAC(3)_Via,dfrA1,ErmB,lnuB,aadA.Actinobacteria was the primary host of ARGs and was suppressed by RSD.Soil physicochemical properties,such as total nitrogen,soil pH,total carbon,were crucial factors affecting ARG profiles.Our findings demonstrated that RSD treatment inhibited pathogenic bacteria and could be an option for reducing high-risk ARG proliferation in soil.展开更多
Coffee wilt represents one of the most devastating diseases of Arabica coffee(Coffea arabica L.)plantations in the primary coffee-producing regions.In this study,coffee trees manifesting wilt symptoms accompanied by t...Coffee wilt represents one of the most devastating diseases of Arabica coffee(Coffea arabica L.)plantations in the primary coffee-producing regions.In this study,coffee trees manifesting wilt symptoms accompanied by the defoliation and drying of the whole tree were observed in the Jazan,El Baha,Najran,and Asir regions.The purpose of this investigation was to isolate and identify the Fusarium species recovered from symptomatic coffee trees.The developed fungi were initially characterized based on their morphological features followed by molecular phylogenetic multi-locus analysis of the combined sequences of ITS,TEF1-α,RPB2,and CaM.Twenty-five isolates were recovered from 28 samples.All fungal isolates were categorized morphologically under the genus Fusarium.Phylogenetic analysis positioned all the representative 15 isolates into one cluster grouping together with Neocosmospora falciformis(formerly F.falciforme)confirming their taxonomic position.Pathogenicity tests of the N.falciformis isolates were subsequently conducted on coffee seedlings,and the results revealed that all isolates induced wilt symptoms resembling those recorded in the field,and the incidence was 100%.The fungicide sensitivity test of seven investigated fungicides revealed that Maxim XL^(®) followed by Moncut^(®) exhibited the highest inhibitory effect against N.falciformis KSA 24-14,reaching 93.33%and 91.67%,respectively.To our knowledge,N.falciformis is a new causal pathogen of coffee wilt in Saudi Arabia.Remarkably,these results offer important insights for devising effective approaches to monitor and control such diseases.展开更多
Electrochemiluminescence(ECL)technology has emerged as a pivotal tool in the field of pathogen detection due to its high sensitivity,strong specificity,operational convenience,and adaptability to complex biological sa...Electrochemiluminescence(ECL)technology has emerged as a pivotal tool in the field of pathogen detection due to its high sensitivity,strong specificity,operational convenience,and adaptability to complex biological samples.This paper systematically elucidates the fundamental mechanisms and classification characteristics of ECL technology,with a particular focus on its applications in detecting nucleic acids,proteins,metabolites,and drug-resistant mutants of pathogenic microorganisms.Through comparative analysis with traditional detection methods,the technological advantages and suitable scenarios of ECL are highlighted.Furthermore,this paper delves into the existing challenges of ECL technology in clinical applications,providing a theoretical basis for advancing its translational use in pathogen diagnostics.展开更多
Hypertrophic cardiomyopathy(HCM)is an autosomal dominant inherited cardiomyopathy characterized by left ventricular hypertrophy.It is one of the chief causes of sudden cardiac death in younger people and athletes.Mole...Hypertrophic cardiomyopathy(HCM)is an autosomal dominant inherited cardiomyopathy characterized by left ventricular hypertrophy.It is one of the chief causes of sudden cardiac death in younger people and athletes.Molecular-genetic studies have confirmed that the vast majority of HCM is caused by mutations in genes encoding sarcomere proteins.HCM has a relatively wide phenotypic heterogeneity,varying from asymptomatic to sudden cardiac death,because of the many different mutations and pathogenic genes underlying it.Many studies have explored the clinical symptoms and prognosis of HCM,emphasizing the importance of genotype in evaluating patient prognosis and guiding the clinical management of HCM.To elaborate the main pathogenic genes and phenotypic prognosis in HCM to promote a better understanding of this genetic disease.Retrospective analysis of literature to evaluate the association between underlying gene mutations and clinical phenotypes in HCM patients.As sequencing technology advances,the pathogenic gene mutation spectrum and phenotypic characteristics of HCM are gradually becoming clearer.HCM is a widespread inherited disease with a highly variable clinical phenotype.The precise mechanisms linking known pathogenic gene mutations and the clinical course of this heterogeneous condition remain elusive.展开更多
Grape white rot caused by Coniella vitis is a global concern in the grape industry.pH regulation is essential for cell growth,reproductive processes and pathogenicity in phytopathogenic fungi.In this study,we observed...Grape white rot caused by Coniella vitis is a global concern in the grape industry.pH regulation is essential for cell growth,reproductive processes and pathogenicity in phytopathogenic fungi.In this study,we observed that the growth rate,spore production and virulence of C.vitis significantly declined in alkaline pH,as well as the suppressive effect on secretion of hydrolytic enzymes.Transcriptomic and metabolomic analyses were used to investigate the responses of C.vitis to acidic(pH 5),neutral(pH 7)and alkaline environments(pH 9).We identified 728,1,780 and 3,386 differentially expressed genes(DEGs)at pH 5,pH 7 and pH 9,when compared with the host pH(pH 3),and 2,122 differently expressed metabolites(DEMs)in negative and positive ion mode.Most DEGs were involved in carbohydrate metabolic process,transmembrane transport,tricarboxylic acid cycle,peptide metabolic process,amide biosynthetic process,and organic acid metabolic process.In addition,metabolomic analysis revealed ABC transporters,indole alkaloid biosynthesis,diterpenoid biosynthesis,and carotenoid biosynthesis pathways in response to the pH change.Furthermore,we found that the aspartate synthesis metabolic route associated with the TCA cycle is a key limiting factor for the growth and development of C.vitis in alkaline environments,and aspartate supplementation enables C.vitis to grow in alkaline environments.Plant cell wall-degrading enzymes(PCWDEs)could contribute to the pathogenicity,when C.vitis infected at pH 3.Importantly,aflatrem biosynthesis in acidic environment might contribute to the virulence of C.vitis and has a risk of causing human health problems due to its acute neurotoxic effects.展开更多
Magnaporthe oryzae is the causal agent of rice blast. Glycosylation plays key roles in vegetative growth,development, and infection of M. oryzae. However, several glycosylation-related genes have not been characterize...Magnaporthe oryzae is the causal agent of rice blast. Glycosylation plays key roles in vegetative growth,development, and infection of M. oryzae. However, several glycosylation-related genes have not been characterized.In this study, we identified a Glyco_transf_22 domain-containing protein, MoAlg9, and found that MoAlg9 islocalized to the endoplasmic reticulum(ER). Deletion of MoALG9 significantly affected conidial production, normalappressorium formation, responses to stressors, and pathogenicity of M. oryzae. We also found that the ΔMoalg9mutant was defective in glycogen utilization, appressorial penetration, and invasive growth in host cells. Moreover,we further demonstrated that MoALG9 regulates the transcription of several target genes involved in conidiation,appressorium formation, and cell wall integrity. In addition, we found that the Glyco_transf_22 domain is essentialfor normal MoAlg9 function and localization. We also provide evidence that MoAlg9 is involved in N-glycosylationpathway in M. oryzae. Taken together, these results show that MoAlg9 is important for conidiation, appressoriumformation, maintenance of cell wall integrity, and the pathogenesis of M. oryzae.展开更多
Background:New variants of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)continue to drive global epidemics and pose significant health risks.The pathogenicity of these variants evolves under immune press...Background:New variants of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)continue to drive global epidemics and pose significant health risks.The pathogenicity of these variants evolves under immune pressure and host factors.Understanding these changes is crucial for epidemic control and variant research.Methods:Human angiotensin-converting enzyme 2(hACE2)transgenic mice were in-tranasally challenged with the original strain WH-09 and the variants Delta,Beta,and Omicron BA.1,while BALB/c mice were challenged with Omicron subvariants BA.5,BF.7,and XBB.1.To compare the pathogenicity differences among variants,we con-ducted a comprehensive analysis that included clinical symptom observation,meas-urement of viral loads in the trachea and lungs,evaluation of pulmonary pathology,analysis of immune cell infiltration,and quantification of cytokine levels.Results:In hACE2 mice,the Beta variant caused significant weight loss,severe lung inflammation,increased inflammatory and chemotactic factor secretion,greater mac-rophage and neutrophil infiltration in the lungs,and higher viral loads with prolonged shedding duration.In contrast,BA.1 showed a significant reduction in pathogenicity.The BA.5,BF.7,and XBB.1 variants were less pathogenic than the WH-09,Beta,and Delta variants when infected in BALB/c mice.This was evidenced by reduced weight loss,diminished pulmonary pathology,decreased secretion of inflammatory factors and chemokines,reduced macrophage and neutrophil infiltration,as well as lower viral loads in both the trachea and lungs.Conclusion:In hACE2 mice,the Omicron variant demonstrated the lowest pathogenic-ity,while the Beta variant exhibited the highest.Pathogenicity of the Delta variant was comparable to the original WH-09 strain.Among BALB/c mice,Omicron subvari-ants BA.5,BF.7,and XBB.1 showed no statistically significant differences in virulence.展开更多
Major facilitator superfamily(MFS)transporters are secondary active membrane transporters that play an important role in solute interchange and energy metabolism.Peronophythora litchii causes the most destructive dise...Major facilitator superfamily(MFS)transporters are secondary active membrane transporters that play an important role in solute interchange and energy metabolism.Peronophythora litchii causes the most destructive disease on lichi,litchi downy blight.PlM90 was reported as a key oosporogenesis regulator.Here,we identified an MFS transporter gene PlMFS1,which is up-regulated during oospore formation at the late infection stage,while down-regulated in the PlM90 mutant.To investigate PlMFS1 function,we generated PlMFS1knockout mutants using CRISPR/Cas9-mediated genome editing technology.Compared with the wild-type strain SHS3,PlMFS1 deletion impaired mycelium growth,zoospore release,oospore production and pathogenicity.Furthermore,PlMFS1 deletion significantly affected P.litchii utilization of fructose,lactose and maltose,and may be the PlMFS1 mechanism involved in mycelial growth.PlMFS1 gene deletion also led to deceased laccase activity,laccase-encoding gene downregulation and impaired P.litchii pathogenicity.To our knowledge,this is the first report of an MFS transporter involved in sugar utilization,sexual reproduction,asexual reproduction and pathogenesis in oomycetes.展开更多
In order to ensure food safety,controlling foodborne pathogen contamination is of utmost importance.Growing apprehensions regarding the safety of synthetic antimicrobials,due to their adverse health effects,have promp...In order to ensure food safety,controlling foodborne pathogen contamination is of utmost importance.Growing apprehensions regarding the safety of synthetic antimicrobials,due to their adverse health effects,have prompted a search for alternative options.Plant natural products(PNPs)with antimicrobial activity are being explored as a viable alternative.Among the various antimicrobial natural products studied,plant essential oils,plant flavonoids,plant polyphenols,plant polysaccharides,and plant antimicrobial peptides have been identified as potential candidates.PNPs demonstrate a diverse array of antimicrobial mechanisms,encompassing cell wall and membrane damage,interference with genetic replication,disruption of energy metabolism,and induction of oxidative stress at the single-cell level,as well as inhibition of biofilm formation and quorum sensing at the population level.Certain PNPs have been harnessed as natural antimicrobial agents for the food preservation.The utilization of encapsulation technology proves to be an effective strategy in protecting PNPs,thereby ensuring good antimicrobial efficacy,enhanced dispersibility,and controlled release within food products.The utilization of nanoemulsions,nanoliposomes,edible packaging,electrospun nanofibers,and microcapsules formed by encapsulation has enriched the ways in which PNPs can be applied in food preservation.Although PNPs have great potential in food preservation,their widespread application in the food industry is currently constrained by factors such as production costs,safety concerns,and legal considerations.Chemical synthesis and biosynthesis pathways offer viable strategies for reducing the cost of producing PNPs,and ongoing efforts to assess safety and improve regulatory frameworks are likely to facilitate the broader adoption of PNPs in food preservation practices.This article provides an overview of the main types of PNPs with antimicrobial activity and their properties,focusing on their mechanisms of action.Additionally,it summarizes the use of PNPs in food preservation and discusses the characteristics and applications of different encapsulation technologies.Lastly,the paper briefly analyzes current limitations and proposes potential future trends for this field.展开更多
Ceratocystis fimbriata is a hazardous fungal pathogen that causes black rot disease in sweet potato roots,leading to devastating losses during sweet potato growth and storage.All methods for managing C.fimbriata on sw...Ceratocystis fimbriata is a hazardous fungal pathogen that causes black rot disease in sweet potato roots,leading to devastating losses during sweet potato growth and storage.All methods for managing C.fimbriata on sweet potato based on synthetic fungicides,biocontrol agents,coatings,and natural compounds are reviewed for the first time.The advantages and disadvantages of the different methods are discussed,and their efficacies are compared.Bacillus strains and the synthetic fungicides carbendazim,flutriafol,liguoling,Stadium?,thiabendazole,and thiophanate methyl show the strongest inhibitory effects.Bacillus strains possess an advantage over synthetic fungicides due to the detrimental impact of the latter on human health.The application of filamentous fungi and yeasts as biocontrol agents for C.fimbriata management has not yet been investigated.Coatings exhibit limited protection,and no attempts have been made to combine coatings with nanoparticles or essential oils.Although the natural compounds perillaldehyde and nerol are inexpensive and non-toxic,they are of low efficacy.All management strategies have been used on postharvest sweet potato roots and leaves.However,there is no approach to controlling C.fimbriata in roots during plant growth.Even though several methods for controlling C.fimbriata on sweet potato have been reported in recent years,numerous knowledge gaps impede the development of effective and safe approaches.展开更多
In Candida species,the endoplasmic reticulum(ER)stress response—regulated by the unfolded protein response(UPR)—serves as a critical adaptive mechanism affecting both pathogenicity and antifungal resistance.This rev...In Candida species,the endoplasmic reticulum(ER)stress response—regulated by the unfolded protein response(UPR)—serves as a critical adaptive mechanism affecting both pathogenicity and antifungal resistance.This review aims to synthesize current knowledge on ER stress pathways in Candida glabrata and Candida albicans,highlighting their species-specific adaptations and therapeutic implications.We systematically analyzed peer-reviewed literature on ER stress mechanisms in Candida,focusing on comparative studies of UPR signaling.Emphasis was placed on C.glabrata’s inositol-requiring enzyme 1(IRE1)-dependent Regulated IRE1-Dependent Decay(RIDD)pathway and C.albicans’IRE1/HAC1 and calcium-mediated pathways.Connections to virulence and drug resistance were evaluated through genetic,transcriptomic,and phenotypic evidence.Candida species employ divergent UPR strategies:C.glabrata mitigates ER stress primarily via RIDD-mediated mRNA decay to reduce protein load,while C.albicans enhances folding capacity through HAC1 splicing and calcium homeostasis.These adaptations promote survival in hostile host environments(e.g.,oxidative stress,immune attacks)and are linked to resistance against azoles and echinocandins.Pharmacological disruption of UPR components(e.g.,IRE1 inhibitors)sensitizes Candida to antifungals in experimental models.ER stress response pathways are promising targets for antifungal drug development.Understanding species-specific UPR mechanisms in Candida could guide novel therapies to overcome resistance and improve treatment outcomes.展开更多
In order to better implement the“Three-Dimensional Education”and cultivate high-quality nursing talents,the integration of ideological and political education into the pathogen biology curriculum promotes curriculum...In order to better implement the“Three-Dimensional Education”and cultivate high-quality nursing talents,the integration of ideological and political education into the pathogen biology curriculum promotes curriculum reform and application.This article explores the use of various teaching methods and means in the teaching process of pathogen biology under the guidance of ideological and political education,aiming to stimulate students’learning interest,cultivate their autonomous learning ability,independent thinking,problem-analyzing and problem-solving abilities,and thus improve their comprehensive qualities and medical professional literacy.展开更多
The giant African snail(Achatina fulica)is an invasive species served as potential vectors for antibiotic resistance genes(ARGs)and potential human bacterial pathogens.Currently,urban green spaces receive extensive or...The giant African snail(Achatina fulica)is an invasive species served as potential vectors for antibiotic resistance genes(ARGs)and potential human bacterial pathogens.Currently,urban green spaces receive extensive organic manure additions as part of their management,may intensify the biological contamination potential of these snail vectors,thereby increasing the risk of biological pollution in green spaces.However,the specific impacts of this practice on the microbial ecology of these invasive species remain poorly understood.Here,we investigated the effects of organic manure application on the gut microbiome of giant African snails,focusing on ARGs,bacterial community structure,and potential human bacterial pathogens.Microcosm experiments compared snail gut microbiomes in different treatments(Soil:soil samples collected after manure amendment,before any snail exposure.Feces:fecal samples collected from snails that lived on manure-amended soil.Control:fecal samples collected from snails that lived on unamended soil)using 16S r RNA high-throughput sequencing and metagenomic analysis.Our results show that manure application significantly altered gut bacterial community structure and increased ARG diversity by enriching specific high-risk ARGs(such as sul1 and sul2 in the Feces group increased by 2.89 and 2.43 times,respectively,compared to the Control group),and the introduction of eight novel ARG subtypes,despite decreasing overall ARG abundance.Moreover,the relative abundance of potential human pathogens,particularly Pseudomonadaceae,was greatly increased by manure application.These findings reveal that organic manure application in urban green spaces can potentially enhances their role as reservoirs and vectors of ARGs and human pathogens.展开更多
Granulicatella species,previously classified as nutritionally variant streptococci,have emerged as important opportunistic pathogens.Although typically part of the normal oral,gastrointestinal,and genitourinary flora,...Granulicatella species,previously classified as nutritionally variant streptococci,have emerged as important opportunistic pathogens.Although typically part of the normal oral,gastrointestinal,and genitourinary flora,these fastidious Gram-positive cocci can cause serious infections in both immunocompetent and immunocompromised individuals.Their identification often proves difficult due to slow growth and unusual nutritional requirements,which limit the reliability of conventional culture methods.This narrative review consolidates data from over 100 case reports and clinical studies to present a comprehensive overview of Granulicatella infections.Infective endocarditis appears as the most frequently reported and life-threatening condition,often affecting the aortic and mitral valves.Patients with prosthetic valves or congenital heart defects face a higher risk.Delayed diagnosis frequently results in complications such as heart failure,systemic emboli,and renal dysfunction.Granulicatella species also contribute to osteomyelitis,pulmonary infections,brain abscesses,gastrointestinal sepsis,and infections related to implanted medical devices.Effective management typically involves beta-lactam antibiotics combined with aminoglycosides,although antimicrobial resistance remains a concern.Surgical intervention often proves necessary,especially in cases with prosthetic material or severe complications.Outcomes are generally favorable when infections are identified early and managed effectively.However,delayed recognition and suboptimal therapy continue to contribute to poor prognoses in some patients.This review emphasizes the need to improve clinical awareness and establish standardized diagnostic and therapeutic approaches to address the challenges posed by Granulicatella infections.展开更多
Avian pathogenic Escherichia coli(APEC)belonging to extraintestinal pathogenic E.coli(ExPEC)can cause severe infections in extraintestinal tissues in birds and humans,such as the lungs and blood.MprA(microcin producti...Avian pathogenic Escherichia coli(APEC)belonging to extraintestinal pathogenic E.coli(ExPEC)can cause severe infections in extraintestinal tissues in birds and humans,such as the lungs and blood.MprA(microcin production regulation,locus A,herein renamed AbsR,a blood survival regulator),a member of the MarR(multiple antibiotic resistance regulator)transcriptional regulator family,governs the expression of capsule biosynthetic genes in human ExPEC and represents a promising druggable target for antimicrobials.However,a deep understanding of the AbsR regulatory mechanism as well as its regulon is lacking.In this study,we present a systems-level analysis of the APEC AbsR regulon using ChIP-Seq(chromatin immunoprecipitation sequencing)and RNA-Seq(RNA sequencing)methods.We found that AbsR directly regulates 99 genes and indirectly regulates 667 genes.Furthermore,we showed that:1)AbsR contributes to antiphagocytotic effects by macrophages and virulence in a mouse model for systemic infection by directly activating the capsular gene cluster;2)AbsR positively impacts biofilm formation via direct regulation of the T2SS(type II secretion system)but plays a marginal role in virulence;and 3)AbsR directly upregulates the acid tolerance signaling system EvgAS to withstand acid stress but is dispensable in ExPEC virulence.Finally,our data indicate that the role of AbsR in virulence gene regulation is relatively conserved in ExPEC strains.Altogether,this study provides a comprehensive analysis of the AbsR regulon and regulatory mechanism,and our data suggest that AbsR likely influences virulence primarily through the control of capsule production.Interestingly,we found that AbsR severely represses the expression of the type I-F CRISPR(clustered regularly interspaced short palindromic repeats)-Cas(CRISPR associated)systems,which could have implications in CRISPR biology and application.展开更多
Blast disease,caused by the hemibiotrophic ascomycete fungus,Magnaporthe oryzae,is a significant threat to sustainable rice production worldwide.Studies have shown that the blast fungus secretes vast arrays of functio...Blast disease,caused by the hemibiotrophic ascomycete fungus,Magnaporthe oryzae,is a significant threat to sustainable rice production worldwide.Studies have shown that the blast fungus secretes vast arrays of functionally diverse proteins into the host cell for a successful disease progression.However,the final destinations of these effector proteins inside the host cell and their role in advancing fungal pathogenesis remain a mystery.Here,we reported that a putative mitochondrial targeting non-classically secreted protein(MoMtp)positively regulates conidiogenesis and appressorium maturation in M.oryzae.Moreover,MoM TP gene deletion mutant strains triggered a hypersensitive response when inoculated on rice leaves displaying that MoMtp is essential for the virulence of M.oryzae.In addition,cell wall and oxidative stress results indicated that MoMtp is likely involved in the maintenance of the structural integrity of the fungus cell.Our study also demonstrates an upregulation in the expression pattern of the MoMTP gene at all stages of infection,indicating its possible regulatory role in host invasion and the infectious development of M.oryzae.Furthermore,Agrobacterium infiltration and sheath inoculation confirmed that MoMtpGFP protein is predominantly localized in the host mitochondria of tobacco leaf and rice cells.Taken together,we conclude that MoMtp protein likely promotes the normal conidiation and pathogenesis of M.oryzae and might have a role in disturbing the proper functioning of the host mitochondria during pathogen invasion.展开更多
The recent concurrent emergence of H5N1,H5N6,and H5N8 avian influenza viruses(AIVs)has led to significant avian mortality globally.Since 2020,frequent human-animal interactions have been documented.To gain insight int...The recent concurrent emergence of H5N1,H5N6,and H5N8 avian influenza viruses(AIVs)has led to significant avian mortality globally.Since 2020,frequent human-animal interactions have been documented.To gain insight into the novel H5 subtype AIVs(i.e.,H5N1,H5N6 and H5N8),we collected 6102 samples from various regions of China between January 2021 and September 2022,and identified 41 H5Nx strains.Comparative analyses on the evolution and biological properties of these isolates were conducted.Phylogenetic analysis revealed that the 41 H5Nx strains belonged to clade 2.3.4.4b,with 13 related to H5N1,19 to H5N6,and 9 to H5N8.Analysis based on global 2.3.4.4b viruses showed that all the viruses described in this study were likely originated from H5N8,exhibiting a heterogeneous evolutionary history between H5N1 and H5N6 during 2015–2022 worldwide.H5N1 showed a higher rate of evolution in 2021–2022 and more sites under positive selection pressure in 2015–2022.The antigenic profiles of the novel H5N1 and H5N6 exhibited notable variations.Further hemagglutination inhibition assay suggested that some A(H5N1)viruses may be antigenically distinct from the circulating H5N6 and H5N8 strains.Mammalian challenge assays demonstrated that the H5N8 virus(21GD001_H5N8)displayed the highest pathogenicity in mice,followed by the H5N1 virus(B1557_H5N1)and then the H5N6 virus(220086_H5N6),suggesting a heterogeneous virulence profile of H5 AIVs in the mammalian hosts.Based on the above results,we speculate that A(H5N1)viruses have a higher risk of emergence in the future.Collectively,these findings unveil a new landscape of different evolutionary history and biological characteristics of novel H5 AIVs in clade 2.3.4.4b,contributing to a better understanding of designing more effective strategies for the prevention and control of novel H5 AIVs.展开更多
基金supported by the National KeyR&DProgramof China(2022YFF0710500)the National Natural Science Foundation of China(32172853 and 32373013)the Central Public-interest Scientific Institution Basal Research Fund,China(1610302022001).
文摘The Salmonella pathogenicity islands(SPIs) play crucial roles in the progression of Salmonella infection. In this study, we constructed an improved λ Red homologous recombination system to prepare single and triple deletion mutants of 3 prominent SPIs(SPI-1, 2, and 3), aiming at the impact of deletion on morphology, carbon source metabolism, adhesion and invasion capacity, in vivo colonization, and immune efficacy in chicks. Our examination revealed that the surface of the single deletion mutants(SM6ΔSPI1, ΔSPI2, and ΔSPI3) exhibited a more rugged texture and appeared to be enveloped in a layer of transparent colloid, whereas the morphology of the triple deletion mutant(SM6ΔSPI1&2&3) remained unaltered when compared to the parent strain. The carbon metabolic spectrum of the SPI mutants underwent profound alterations, with a notable and statistically significant modification observed in 30 out of 95 carbon sources, primarily carbohydrates(17 out of 30). Furthermore, the adhesion capacity of the 4 mutants to Caco-2 cells was significantly reduced when compared to that of the parent strain. Moreover,the invasion capacity of mutants SM6ΔSPI1 and SM6ΔSPI1&2&3 exhibited a substantial decrease, while it was enhanced to varying degrees for SM6ΔSPI3 and SM6ΔSPI2. Importantly, none of the 4 mutants induced any clinical symptoms in the chicks. However, they did transiently colonize the spleen and liver. Notably, the SM6ΔSPI1&2&3mutant was rapidly cleared from both the spleen and liver within 8 days post-infection and no notable pathological changes were observed in the organs. Additionally, when challenged, the mutants immunized groups displayed a significant increase in antibody levels and alterations in the CD3+CD4+ and CD3+CD8+ subpopulations, and the levels of IL-4 and IFN-γ cytokines in the SM6ΔSPI1&2&3 immunized chicken serum surpassed those of other groups.In summary, the successful construction of the 4 SPI mutants lays the groundwork for further exploration into the pathogenic(including metabolic) mechanisms of SPIs and the development of safe and effective live attenuated Salmonella vaccines or carriers.
基金supported by Zhejiang Province Science and Technology Cooperation Project of“Three Rural and Nine Parties”(grant number 2023SNJF059).
文摘Dear Editor,The highly pathogenic avian influenza viruses(HPAIVs)are important epizootic and zoonotic pathogens that cause significant economic losses to the poultry industry and pose a serious risk to veterinary and public health.Wild birds have been recognized as the primary reservoirs for influenza A virus,and some species show little sign of clinical disease or even can be asymptomatic during long distance carriers of the virus(Lycett et al.,2019).Since it was first discovered in 1959,the H5Nx HPAIVs have spread globally and cause outbreaks in wild birds,poultry and sporadic human and other mammalian infections(Lycett et al.,2019).Due to the reassortant events of diverse strains facilitated by migratory waterfowl,the clade 2.3.4.4 of H5Nx viruses acquiring neuraminidase(NA)gene from other low pathogenicity avian influenza viruses(LPAIVs)emerged in 2014 and gradually became the dominant sub-clade(Lee et al.,2017).
基金supported by the Beijing Science and Technology Planning Project of the Beijing Science and Technology Commission(Z241100009024047)the High-Level Public Health Technical Talent Training Plan(lingjunrencai-01-02).
文摘Respiratory infections are associated with high morbidity and mortality and are a major global health problem[1].Acute respiratory infections are caused by multiple respiratory pathogens,including viruses and bacteria.Viral-bacterial co-infections,which have become increasingly common and a global concern,can lead to substantial complications,causing higher morbidity and adverse prognosis[2].Previous studies have reported low positive detection rates of targeted pathogens related to acute respiratory infections,owing to the limited number of detected pathogens and variations in the sensitivity of diagnostic methods[3-4].Low positive detection rates may impede our understanding of respiratory pathogen characteristics and hamper the development of precise treatment and prevention strategies.
基金supported by the Key Research and Development Program of Shandong Province,China(No 2021CXGC010803)Pan’an County Chinese Medicine Industry Project(No.PZYF202103).
文摘Reductive soil disinfestation(RSD)is commonly employed for soil remediation in greenhouse cultivation.However,its influence on antibiotic resistance genes(ARGs)in soil remains uncertain.This study investigated the dynamic changes in soil communities,potential bacterial pathogens,and ARG profiles under various organicmaterial treatments during RSD,including distillers’grains,potato peel,peanut vine,and peanut vine combined with charcoal.Results revealed that applying diverse organic materials in RSD significantly altered bacterial community composition and diminished the relative abundance of potential bacterial pathogens(P<0.05).The relative abundance of high-risk ARGs decreased by 10.7%-30.6%after RSD treatments,the main decreased ARG subtypeswere AAC(3)_Via,dfrA1,ErmB,lnuB,aadA.Actinobacteria was the primary host of ARGs and was suppressed by RSD.Soil physicochemical properties,such as total nitrogen,soil pH,total carbon,were crucial factors affecting ARG profiles.Our findings demonstrated that RSD treatment inhibited pathogenic bacteria and could be an option for reducing high-risk ARG proliferation in soil.
基金funded by the Deanship of Scientific Research,Vice Presidency for Graduate Studies and Scientific Research,King Faisal University,Saudi Arabia,for supporting this work for work through grant number KFU242134.
文摘Coffee wilt represents one of the most devastating diseases of Arabica coffee(Coffea arabica L.)plantations in the primary coffee-producing regions.In this study,coffee trees manifesting wilt symptoms accompanied by the defoliation and drying of the whole tree were observed in the Jazan,El Baha,Najran,and Asir regions.The purpose of this investigation was to isolate and identify the Fusarium species recovered from symptomatic coffee trees.The developed fungi were initially characterized based on their morphological features followed by molecular phylogenetic multi-locus analysis of the combined sequences of ITS,TEF1-α,RPB2,and CaM.Twenty-five isolates were recovered from 28 samples.All fungal isolates were categorized morphologically under the genus Fusarium.Phylogenetic analysis positioned all the representative 15 isolates into one cluster grouping together with Neocosmospora falciformis(formerly F.falciforme)confirming their taxonomic position.Pathogenicity tests of the N.falciformis isolates were subsequently conducted on coffee seedlings,and the results revealed that all isolates induced wilt symptoms resembling those recorded in the field,and the incidence was 100%.The fungicide sensitivity test of seven investigated fungicides revealed that Maxim XL^(®) followed by Moncut^(®) exhibited the highest inhibitory effect against N.falciformis KSA 24-14,reaching 93.33%and 91.67%,respectively.To our knowledge,N.falciformis is a new causal pathogen of coffee wilt in Saudi Arabia.Remarkably,these results offer important insights for devising effective approaches to monitor and control such diseases.
基金supported by the Joint Funds for the innovation of science and Technology,Fujian province(Grant number:2021Y9014).
文摘Electrochemiluminescence(ECL)technology has emerged as a pivotal tool in the field of pathogen detection due to its high sensitivity,strong specificity,operational convenience,and adaptability to complex biological samples.This paper systematically elucidates the fundamental mechanisms and classification characteristics of ECL technology,with a particular focus on its applications in detecting nucleic acids,proteins,metabolites,and drug-resistant mutants of pathogenic microorganisms.Through comparative analysis with traditional detection methods,the technological advantages and suitable scenarios of ECL are highlighted.Furthermore,this paper delves into the existing challenges of ECL technology in clinical applications,providing a theoretical basis for advancing its translational use in pathogen diagnostics.
基金Supported by National Natural Science Foundation of China,No.81770379 and 81470521.
文摘Hypertrophic cardiomyopathy(HCM)is an autosomal dominant inherited cardiomyopathy characterized by left ventricular hypertrophy.It is one of the chief causes of sudden cardiac death in younger people and athletes.Molecular-genetic studies have confirmed that the vast majority of HCM is caused by mutations in genes encoding sarcomere proteins.HCM has a relatively wide phenotypic heterogeneity,varying from asymptomatic to sudden cardiac death,because of the many different mutations and pathogenic genes underlying it.Many studies have explored the clinical symptoms and prognosis of HCM,emphasizing the importance of genotype in evaluating patient prognosis and guiding the clinical management of HCM.To elaborate the main pathogenic genes and phenotypic prognosis in HCM to promote a better understanding of this genetic disease.Retrospective analysis of literature to evaluate the association between underlying gene mutations and clinical phenotypes in HCM patients.As sequencing technology advances,the pathogenic gene mutation spectrum and phenotypic characteristics of HCM are gradually becoming clearer.HCM is a widespread inherited disease with a highly variable clinical phenotype.The precise mechanisms linking known pathogenic gene mutations and the clinical course of this heterogeneous condition remain elusive.
基金supported by the Shandong Provincial Natural Science Foundation,China(ZR2021QC131)the Shandong Province Key Research and Development Plan,China(2022TZXD001102)+1 种基金the Shandong Province Demonstration Project for Model Construction in Rural Revitalization Service,China(2022DXAL0226)the Innovation Project of Shandong Academy of Agricultural Sciences,China(CXGC2023F15,CXGC2023A41,and CXGC2023A47)。
文摘Grape white rot caused by Coniella vitis is a global concern in the grape industry.pH regulation is essential for cell growth,reproductive processes and pathogenicity in phytopathogenic fungi.In this study,we observed that the growth rate,spore production and virulence of C.vitis significantly declined in alkaline pH,as well as the suppressive effect on secretion of hydrolytic enzymes.Transcriptomic and metabolomic analyses were used to investigate the responses of C.vitis to acidic(pH 5),neutral(pH 7)and alkaline environments(pH 9).We identified 728,1,780 and 3,386 differentially expressed genes(DEGs)at pH 5,pH 7 and pH 9,when compared with the host pH(pH 3),and 2,122 differently expressed metabolites(DEMs)in negative and positive ion mode.Most DEGs were involved in carbohydrate metabolic process,transmembrane transport,tricarboxylic acid cycle,peptide metabolic process,amide biosynthetic process,and organic acid metabolic process.In addition,metabolomic analysis revealed ABC transporters,indole alkaloid biosynthesis,diterpenoid biosynthesis,and carotenoid biosynthesis pathways in response to the pH change.Furthermore,we found that the aspartate synthesis metabolic route associated with the TCA cycle is a key limiting factor for the growth and development of C.vitis in alkaline environments,and aspartate supplementation enables C.vitis to grow in alkaline environments.Plant cell wall-degrading enzymes(PCWDEs)could contribute to the pathogenicity,when C.vitis infected at pH 3.Importantly,aflatrem biosynthesis in acidic environment might contribute to the virulence of C.vitis and has a risk of causing human health problems due to its acute neurotoxic effects.
基金supported by the National Natural Science Foundation of China (32202253)the Natural Science Foundation of Anhui Higher Education Institutions, China (KJ2020A0102)the Talent Research Project of Anhui Agricultural University, China (rc342001)。
文摘Magnaporthe oryzae is the causal agent of rice blast. Glycosylation plays key roles in vegetative growth,development, and infection of M. oryzae. However, several glycosylation-related genes have not been characterized.In this study, we identified a Glyco_transf_22 domain-containing protein, MoAlg9, and found that MoAlg9 islocalized to the endoplasmic reticulum(ER). Deletion of MoALG9 significantly affected conidial production, normalappressorium formation, responses to stressors, and pathogenicity of M. oryzae. We also found that the ΔMoalg9mutant was defective in glycogen utilization, appressorial penetration, and invasive growth in host cells. Moreover,we further demonstrated that MoALG9 regulates the transcription of several target genes involved in conidiation,appressorium formation, and cell wall integrity. In addition, we found that the Glyco_transf_22 domain is essentialfor normal MoAlg9 function and localization. We also provide evidence that MoAlg9 is involved in N-glycosylationpathway in M. oryzae. Taken together, these results show that MoAlg9 is important for conidiation, appressoriumformation, maintenance of cell wall integrity, and the pathogenesis of M. oryzae.
基金National Science and Technology Infrastructure of China,Grant/Award Number:National Pathogen Resource Center-NPRC-32National Key Research and Development Program of China,Grant/Award Number:2023YFF0724800CAMS Innovation Fund for Medical Sciences,Grant/Award Number:2021-I2M-1-035。
文摘Background:New variants of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)continue to drive global epidemics and pose significant health risks.The pathogenicity of these variants evolves under immune pressure and host factors.Understanding these changes is crucial for epidemic control and variant research.Methods:Human angiotensin-converting enzyme 2(hACE2)transgenic mice were in-tranasally challenged with the original strain WH-09 and the variants Delta,Beta,and Omicron BA.1,while BALB/c mice were challenged with Omicron subvariants BA.5,BF.7,and XBB.1.To compare the pathogenicity differences among variants,we con-ducted a comprehensive analysis that included clinical symptom observation,meas-urement of viral loads in the trachea and lungs,evaluation of pulmonary pathology,analysis of immune cell infiltration,and quantification of cytokine levels.Results:In hACE2 mice,the Beta variant caused significant weight loss,severe lung inflammation,increased inflammatory and chemotactic factor secretion,greater mac-rophage and neutrophil infiltration in the lungs,and higher viral loads with prolonged shedding duration.In contrast,BA.1 showed a significant reduction in pathogenicity.The BA.5,BF.7,and XBB.1 variants were less pathogenic than the WH-09,Beta,and Delta variants when infected in BALB/c mice.This was evidenced by reduced weight loss,diminished pulmonary pathology,decreased secretion of inflammatory factors and chemokines,reduced macrophage and neutrophil infiltration,as well as lower viral loads in both the trachea and lungs.Conclusion:In hACE2 mice,the Omicron variant demonstrated the lowest pathogenic-ity,while the Beta variant exhibited the highest.Pathogenicity of the Delta variant was comparable to the original WH-09 strain.Among BALB/c mice,Omicron subvari-ants BA.5,BF.7,and XBB.1 showed no statistically significant differences in virulence.
基金funded by the Natural Science Foundation of Guangdong Province,China(Grant Nos.2023A1515012617,2022A1515010458 and 2023A1515030267)Guangzhou Science&Technology Program(Grant No.202201010410)the earmarked fund for CARS-32。
文摘Major facilitator superfamily(MFS)transporters are secondary active membrane transporters that play an important role in solute interchange and energy metabolism.Peronophythora litchii causes the most destructive disease on lichi,litchi downy blight.PlM90 was reported as a key oosporogenesis regulator.Here,we identified an MFS transporter gene PlMFS1,which is up-regulated during oospore formation at the late infection stage,while down-regulated in the PlM90 mutant.To investigate PlMFS1 function,we generated PlMFS1knockout mutants using CRISPR/Cas9-mediated genome editing technology.Compared with the wild-type strain SHS3,PlMFS1 deletion impaired mycelium growth,zoospore release,oospore production and pathogenicity.Furthermore,PlMFS1 deletion significantly affected P.litchii utilization of fructose,lactose and maltose,and may be the PlMFS1 mechanism involved in mycelial growth.PlMFS1 gene deletion also led to deceased laccase activity,laccase-encoding gene downregulation and impaired P.litchii pathogenicity.To our knowledge,this is the first report of an MFS transporter involved in sugar utilization,sexual reproduction,asexual reproduction and pathogenesis in oomycetes.
基金supported by the National Natural Science Foundation of China(32060520)Science and Technology Talents and Platform Program of Yunnan Province(202105AF150049)University Key Laboratory of Food Microbial Resources and Utilization in Yunnan Province(Yunjiaofa[2018]No.135).
文摘In order to ensure food safety,controlling foodborne pathogen contamination is of utmost importance.Growing apprehensions regarding the safety of synthetic antimicrobials,due to their adverse health effects,have prompted a search for alternative options.Plant natural products(PNPs)with antimicrobial activity are being explored as a viable alternative.Among the various antimicrobial natural products studied,plant essential oils,plant flavonoids,plant polyphenols,plant polysaccharides,and plant antimicrobial peptides have been identified as potential candidates.PNPs demonstrate a diverse array of antimicrobial mechanisms,encompassing cell wall and membrane damage,interference with genetic replication,disruption of energy metabolism,and induction of oxidative stress at the single-cell level,as well as inhibition of biofilm formation and quorum sensing at the population level.Certain PNPs have been harnessed as natural antimicrobial agents for the food preservation.The utilization of encapsulation technology proves to be an effective strategy in protecting PNPs,thereby ensuring good antimicrobial efficacy,enhanced dispersibility,and controlled release within food products.The utilization of nanoemulsions,nanoliposomes,edible packaging,electrospun nanofibers,and microcapsules formed by encapsulation has enriched the ways in which PNPs can be applied in food preservation.Although PNPs have great potential in food preservation,their widespread application in the food industry is currently constrained by factors such as production costs,safety concerns,and legal considerations.Chemical synthesis and biosynthesis pathways offer viable strategies for reducing the cost of producing PNPs,and ongoing efforts to assess safety and improve regulatory frameworks are likely to facilitate the broader adoption of PNPs in food preservation practices.This article provides an overview of the main types of PNPs with antimicrobial activity and their properties,focusing on their mechanisms of action.Additionally,it summarizes the use of PNPs in food preservation and discusses the characteristics and applications of different encapsulation technologies.Lastly,the paper briefly analyzes current limitations and proposes potential future trends for this field.
基金supported by the National Natural Science Foundation of China(Nos.32172441,32302433,and 32001599)。
文摘Ceratocystis fimbriata is a hazardous fungal pathogen that causes black rot disease in sweet potato roots,leading to devastating losses during sweet potato growth and storage.All methods for managing C.fimbriata on sweet potato based on synthetic fungicides,biocontrol agents,coatings,and natural compounds are reviewed for the first time.The advantages and disadvantages of the different methods are discussed,and their efficacies are compared.Bacillus strains and the synthetic fungicides carbendazim,flutriafol,liguoling,Stadium?,thiabendazole,and thiophanate methyl show the strongest inhibitory effects.Bacillus strains possess an advantage over synthetic fungicides due to the detrimental impact of the latter on human health.The application of filamentous fungi and yeasts as biocontrol agents for C.fimbriata management has not yet been investigated.Coatings exhibit limited protection,and no attempts have been made to combine coatings with nanoparticles or essential oils.Although the natural compounds perillaldehyde and nerol are inexpensive and non-toxic,they are of low efficacy.All management strategies have been used on postharvest sweet potato roots and leaves.However,there is no approach to controlling C.fimbriata in roots during plant growth.Even though several methods for controlling C.fimbriata on sweet potato have been reported in recent years,numerous knowledge gaps impede the development of effective and safe approaches.
文摘In Candida species,the endoplasmic reticulum(ER)stress response—regulated by the unfolded protein response(UPR)—serves as a critical adaptive mechanism affecting both pathogenicity and antifungal resistance.This review aims to synthesize current knowledge on ER stress pathways in Candida glabrata and Candida albicans,highlighting their species-specific adaptations and therapeutic implications.We systematically analyzed peer-reviewed literature on ER stress mechanisms in Candida,focusing on comparative studies of UPR signaling.Emphasis was placed on C.glabrata’s inositol-requiring enzyme 1(IRE1)-dependent Regulated IRE1-Dependent Decay(RIDD)pathway and C.albicans’IRE1/HAC1 and calcium-mediated pathways.Connections to virulence and drug resistance were evaluated through genetic,transcriptomic,and phenotypic evidence.Candida species employ divergent UPR strategies:C.glabrata mitigates ER stress primarily via RIDD-mediated mRNA decay to reduce protein load,while C.albicans enhances folding capacity through HAC1 splicing and calcium homeostasis.These adaptations promote survival in hostile host environments(e.g.,oxidative stress,immune attacks)and are linked to resistance against azoles and echinocandins.Pharmacological disruption of UPR components(e.g.,IRE1 inhibitors)sensitizes Candida to antifungals in experimental models.ER stress response pathways are promising targets for antifungal drug development.Understanding species-specific UPR mechanisms in Candida could guide novel therapies to overcome resistance and improve treatment outcomes.
文摘In order to better implement the“Three-Dimensional Education”and cultivate high-quality nursing talents,the integration of ideological and political education into the pathogen biology curriculum promotes curriculum reform and application.This article explores the use of various teaching methods and means in the teaching process of pathogen biology under the guidance of ideological and political education,aiming to stimulate students’learning interest,cultivate their autonomous learning ability,independent thinking,problem-analyzing and problem-solving abilities,and thus improve their comprehensive qualities and medical professional literacy.
基金supported by the National Natural Science Foundation of China(Nos.32361143523 and 42407166)the National Key Research and Development Program of China(No.2023YFF1304600)+2 种基金Ningbo S&T project(No.2021-DST-004)the International Partnership Program of Chinese Academy of Sciences(No.322GJHZ2022028FN)the fellowship of China Postdoctoral Science Foundation(No.2022T150635)。
文摘The giant African snail(Achatina fulica)is an invasive species served as potential vectors for antibiotic resistance genes(ARGs)and potential human bacterial pathogens.Currently,urban green spaces receive extensive organic manure additions as part of their management,may intensify the biological contamination potential of these snail vectors,thereby increasing the risk of biological pollution in green spaces.However,the specific impacts of this practice on the microbial ecology of these invasive species remain poorly understood.Here,we investigated the effects of organic manure application on the gut microbiome of giant African snails,focusing on ARGs,bacterial community structure,and potential human bacterial pathogens.Microcosm experiments compared snail gut microbiomes in different treatments(Soil:soil samples collected after manure amendment,before any snail exposure.Feces:fecal samples collected from snails that lived on manure-amended soil.Control:fecal samples collected from snails that lived on unamended soil)using 16S r RNA high-throughput sequencing and metagenomic analysis.Our results show that manure application significantly altered gut bacterial community structure and increased ARG diversity by enriching specific high-risk ARGs(such as sul1 and sul2 in the Feces group increased by 2.89 and 2.43 times,respectively,compared to the Control group),and the introduction of eight novel ARG subtypes,despite decreasing overall ARG abundance.Moreover,the relative abundance of potential human pathogens,particularly Pseudomonadaceae,was greatly increased by manure application.These findings reveal that organic manure application in urban green spaces can potentially enhances their role as reservoirs and vectors of ARGs and human pathogens.
文摘Granulicatella species,previously classified as nutritionally variant streptococci,have emerged as important opportunistic pathogens.Although typically part of the normal oral,gastrointestinal,and genitourinary flora,these fastidious Gram-positive cocci can cause serious infections in both immunocompetent and immunocompromised individuals.Their identification often proves difficult due to slow growth and unusual nutritional requirements,which limit the reliability of conventional culture methods.This narrative review consolidates data from over 100 case reports and clinical studies to present a comprehensive overview of Granulicatella infections.Infective endocarditis appears as the most frequently reported and life-threatening condition,often affecting the aortic and mitral valves.Patients with prosthetic valves or congenital heart defects face a higher risk.Delayed diagnosis frequently results in complications such as heart failure,systemic emboli,and renal dysfunction.Granulicatella species also contribute to osteomyelitis,pulmonary infections,brain abscesses,gastrointestinal sepsis,and infections related to implanted medical devices.Effective management typically involves beta-lactam antibiotics combined with aminoglycosides,although antimicrobial resistance remains a concern.Surgical intervention often proves necessary,especially in cases with prosthetic material or severe complications.Outcomes are generally favorable when infections are identified early and managed effectively.However,delayed recognition and suboptimal therapy continue to contribute to poor prognoses in some patients.This review emphasizes the need to improve clinical awareness and establish standardized diagnostic and therapeutic approaches to address the challenges posed by Granulicatella infections.
基金supported by the National Natural Science Foundation of China Young Scholars Project(31902242)the Agricultural Science and Technology Innovation Program(ASTIP)of Chinese Academy of Agricultural Sciences(2017–2020)。
文摘Avian pathogenic Escherichia coli(APEC)belonging to extraintestinal pathogenic E.coli(ExPEC)can cause severe infections in extraintestinal tissues in birds and humans,such as the lungs and blood.MprA(microcin production regulation,locus A,herein renamed AbsR,a blood survival regulator),a member of the MarR(multiple antibiotic resistance regulator)transcriptional regulator family,governs the expression of capsule biosynthetic genes in human ExPEC and represents a promising druggable target for antimicrobials.However,a deep understanding of the AbsR regulatory mechanism as well as its regulon is lacking.In this study,we present a systems-level analysis of the APEC AbsR regulon using ChIP-Seq(chromatin immunoprecipitation sequencing)and RNA-Seq(RNA sequencing)methods.We found that AbsR directly regulates 99 genes and indirectly regulates 667 genes.Furthermore,we showed that:1)AbsR contributes to antiphagocytotic effects by macrophages and virulence in a mouse model for systemic infection by directly activating the capsular gene cluster;2)AbsR positively impacts biofilm formation via direct regulation of the T2SS(type II secretion system)but plays a marginal role in virulence;and 3)AbsR directly upregulates the acid tolerance signaling system EvgAS to withstand acid stress but is dispensable in ExPEC virulence.Finally,our data indicate that the role of AbsR in virulence gene regulation is relatively conserved in ExPEC strains.Altogether,this study provides a comprehensive analysis of the AbsR regulon and regulatory mechanism,and our data suggest that AbsR likely influences virulence primarily through the control of capsule production.Interestingly,we found that AbsR severely represses the expression of the type I-F CRISPR(clustered regularly interspaced short palindromic repeats)-Cas(CRISPR associated)systems,which could have implications in CRISPR biology and application.
基金funded by the National Natural Science Foundation of China(32172364 to Shihong Zhang and 32272513 to Zonghua Wang)Fujian Agriculture and Forestry University scholarship,China for Wajjiha Batool。
文摘Blast disease,caused by the hemibiotrophic ascomycete fungus,Magnaporthe oryzae,is a significant threat to sustainable rice production worldwide.Studies have shown that the blast fungus secretes vast arrays of functionally diverse proteins into the host cell for a successful disease progression.However,the final destinations of these effector proteins inside the host cell and their role in advancing fungal pathogenesis remain a mystery.Here,we reported that a putative mitochondrial targeting non-classically secreted protein(MoMtp)positively regulates conidiogenesis and appressorium maturation in M.oryzae.Moreover,MoM TP gene deletion mutant strains triggered a hypersensitive response when inoculated on rice leaves displaying that MoMtp is essential for the virulence of M.oryzae.In addition,cell wall and oxidative stress results indicated that MoMtp is likely involved in the maintenance of the structural integrity of the fungus cell.Our study also demonstrates an upregulation in the expression pattern of the MoMTP gene at all stages of infection,indicating its possible regulatory role in host invasion and the infectious development of M.oryzae.Furthermore,Agrobacterium infiltration and sheath inoculation confirmed that MoMtpGFP protein is predominantly localized in the host mitochondria of tobacco leaf and rice cells.Taken together,we conclude that MoMtp protein likely promotes the normal conidiation and pathogenesis of M.oryzae and might have a role in disturbing the proper functioning of the host mitochondria during pathogen invasion.
基金supported by the Science and Technology Program of Guangdong Province(2022B1111010004,2021B1212030015)China Agriculture Research System of MOF and MARA(CARS-41)China National Animal Disease Surveillance and Epidemiological Survey Program(2021–2025)(No.202111).
文摘The recent concurrent emergence of H5N1,H5N6,and H5N8 avian influenza viruses(AIVs)has led to significant avian mortality globally.Since 2020,frequent human-animal interactions have been documented.To gain insight into the novel H5 subtype AIVs(i.e.,H5N1,H5N6 and H5N8),we collected 6102 samples from various regions of China between January 2021 and September 2022,and identified 41 H5Nx strains.Comparative analyses on the evolution and biological properties of these isolates were conducted.Phylogenetic analysis revealed that the 41 H5Nx strains belonged to clade 2.3.4.4b,with 13 related to H5N1,19 to H5N6,and 9 to H5N8.Analysis based on global 2.3.4.4b viruses showed that all the viruses described in this study were likely originated from H5N8,exhibiting a heterogeneous evolutionary history between H5N1 and H5N6 during 2015–2022 worldwide.H5N1 showed a higher rate of evolution in 2021–2022 and more sites under positive selection pressure in 2015–2022.The antigenic profiles of the novel H5N1 and H5N6 exhibited notable variations.Further hemagglutination inhibition assay suggested that some A(H5N1)viruses may be antigenically distinct from the circulating H5N6 and H5N8 strains.Mammalian challenge assays demonstrated that the H5N8 virus(21GD001_H5N8)displayed the highest pathogenicity in mice,followed by the H5N1 virus(B1557_H5N1)and then the H5N6 virus(220086_H5N6),suggesting a heterogeneous virulence profile of H5 AIVs in the mammalian hosts.Based on the above results,we speculate that A(H5N1)viruses have a higher risk of emergence in the future.Collectively,these findings unveil a new landscape of different evolutionary history and biological characteristics of novel H5 AIVs in clade 2.3.4.4b,contributing to a better understanding of designing more effective strategies for the prevention and control of novel H5 AIVs.
