The treatment of Acinetobacter baumannii(A.baumannii)poses significant clinical challenges due to its multidrug/pan-drug resistance.In this study,we isolated a broad-spectrum lytic A.baumannii phage,named P425,from me...The treatment of Acinetobacter baumannii(A.baumannii)poses significant clinical challenges due to its multidrug/pan-drug resistance.In this study,we isolated a broad-spectrum lytic A.baumannii phage,named P425,from medical wastewater,targeting nine multidrug-resistant A.baumannii(MDRAB)with diverse capsular types.Biological characterization revealed that P425 maintains activity at pH range of 3–12 and temperature range of 4–50℃.It resists UV irradiation for 20 minutes,and had an optimal multiplicity of infection(OMOI)is 0.00001.The adsorption kinetics showed that P425 achieves>90%within 10 minutes of incubation,and the one-step growth curve indicated a 10-min latent period,with a burst size of 184 PFU/cell.The genome sequencing results indicated that it harbors a double-stranded DNA genome of 40,583 bp with a GC content of 39.39%.Intergenomic similarity analysis classified it as a novel species within the Friunavirus genus,while electron microscopy results showed that it belongs to the Podoviridae family.Notably,P425 exhibits potent 24-h in vitro inhibitory activity against MDRAB,and demonstrates synergistic effect at an MOI of 0.001 when combined with five classes of antibiotics targeting distinct antimicrobial mechanisms.Safety evaluations confirmed the absence of cytotoxicity,hemolytic activity,or systemic toxicity both in vitro and in vivo.In mouse infection models,P425 can significantly improve the survival rates of mice infected with Ab25(ST1791/KL101).When co-administered with levofloxacin,it achieved 100%protection against mortality and promoted immune recovery.Collectively,P425 is a prospective lytic phage that could offer novel strategies for combating MDRAB infections.展开更多
Staphylococcus aureus (S. aureus) is a bacterial pathogen for humans and animals. These bacteria can resist against many antibiotics and this resistance constitute an alarming worldwide human health threat due to the ...Staphylococcus aureus (S. aureus) is a bacterial pathogen for humans and animals. These bacteria can resist against many antibiotics and this resistance constitute an alarming worldwide human health threat due to the morbidity and mortality. Phage therapy is one of the alternative treatments. The aim of this study was to isolate and characterize lytic phages of S. aureus from different wastewater sources in Bobo-Dioulasso, Burkina Faso. Eight strains of S. aureus were isolated from different clinical samples and were used to isolate phages. The isolation and host range of phages were done by the spot test. Phages were purified by the double-layer method. Similar phages after the determination of the host range were characterized using restriction enzymes. A total of 27 phages were obtained after isolation and purification. Nine of the 27 isolates reported a broad host range (≥67%). The results of enzymatic digestion allowed to consider that all phage isolates that presented the same host range and the same genetic fingerprint are the same phage strain;whereas phages that presented the same host range and different genetic fingerprints are different phage strains. Thus, a total of 15 distinct phages isolates specific to S. aureus were characterized. This study highlighted the abundance and lytic capacity of phages isolated from wastewater from Bobo-Dioulasso’s environment against clinical strains of S. aureus. The lytic capacity of these Staphyphages could be an effective alternative tool to combat bacteria multi-resistance.展开更多
The objective of this study is to quantitatively reveal the main genetic carrier of antibiotic resistance genes(ARGs)for blocking their environmental dissemination.The distribution of ARGs in chromosomes,plasmids,and ...The objective of this study is to quantitatively reveal the main genetic carrier of antibiotic resistance genes(ARGs)for blocking their environmental dissemination.The distribution of ARGs in chromosomes,plasmids,and phages for understanding their respective contributions to the development of antimicrobial resistance in aerobic biofilm consortium under increasing stresses of oxytetracycline,streptomycin,and tigecyclinewere revealed based on metagenomics analysis.Results showed that the plasmids harbored 49.2%-83.9%of resistomes,which was higher(p<0.001)than chromosomes(2.0%-35.6%),and no ARGs were detected in phage contigs under the strict alignment standard of over 80%identity used in this study.Plasmids and chromosomes tended to encode different types of ARGs,whose abundances all increased with the hike of antibiotic concentrations,and the variety of ARGs encoded by plasmids(14 types and 64 subtypes)was higher than that(11 types and 27 subtypes)of chromosomes.The dosing of the three antibiotics facilitated the transposition and recombination of ARGs on plasmids,mediated by transposable and integrable transfer elements,which increased the co-occurrence of associated and unassociated ARGs.The results quantitatively proved that plasmids dominate the proliferation of ARGs in aerobic biofilm driven by antibiotic selection,which should be a key target for blocking ARG dissemination.展开更多
Pseudoalteromonas is a group of marine bacteria widespread in diverse marine sediments,producing a wide range of bioactive compounds.However,only a limited number of Pseudoalteromonas phages have been isolated and stu...Pseudoalteromonas is a group of marine bacteria widespread in diverse marine sediments,producing a wide range of bioactive compounds.However,only a limited number of Pseudoalteromonas phages have been isolated and studied.In this study,a novel lytic Pseudoalteromonas phage,denoted as vB_PalP_Y7,was isolated from sewage samples collected at the Seafood Market in Qingdao,China.vB_PalP_Y7 remained stable across a wide range of temperatures(-20–50℃)and a wide pH range(3–12).The vB_PalP_Y7 phage harbors a linear double-stranded DNA molecule of 57699 base pairs(bp)with a G+C content of 45.90%.Furthermore,it is predicted to contain 58 open reading frames(ORFs).Phylogenetic analysis and protein network relationship analysis revealed low similarity between vB_PalP_Y7 and viruses in the ICTV and IMG/VR4 database,suggesting that vB_PalP_Y7 may be a potential new genus,Miuvirus.This study contributed valuable insights to comprehend the relationship between Pseudoalteromonas phages and their host organisms.展开更多
Enterotoxigenic E.coli is one of the bacterial pathogens contributing to the global resistance crisis in public health and animal husbandry.The problem of antibiotic resistance is becoming more and more serious,and ph...Enterotoxigenic E.coli is one of the bacterial pathogens contributing to the global resistance crisis in public health and animal husbandry.The problem of antibiotic resistance is becoming more and more serious,and phage is con-sidered one of the potential alternatives to antibiotics that could be utilized to treat bacterial infections.Our study isolated and identified a lytic phage PGX1 against multidrug-resistant enterotoxigenic E.coli EC6 strain from sew-age.The phage lysis profile revealed that PGX1 exhibited a lytic effect on multidrug-resistant enterotoxigenic E.coli strains of serotype O60.Through phage whole genome sequencing and bioinformatics analysis,PGX1 was found to be the class Caudoviricetes,family Autographiviridae,genus Teseptimavirus.The length of the PGX1 genome is about 37,009 bp,containing 54 open reading frames(ORFs).Notably,phage PGX1 lacks any lysogenic-related genes or virulence genes.Furthermore,phage PGX1 demonstrates strong adaptability,tolerance,and stability in various pH(pH4-10)and temperatures(4–40°C).The in vivo and in vitro tests demonstrated that phage PGX1 significantly removes and inhibits the formation of multidrug-resistant EC6 biofilm and effectively controls the Galleria mel-lonella larvae and enterotoxigenic E.coli EC6 during mice infection.In conclusion,the above findings demonstrated that phage PGX1 may be a novel antimicrobial agent to control multidrug-resistant E.coli infections.展开更多
Epidemiological studies have indicated that branched-chain amino acids(BCAAs)increased and gut microbiota disordered in type 2 diabetes mellitus(T2DM).This study aimed to investigate the mechanism of Lactiplantibacill...Epidemiological studies have indicated that branched-chain amino acids(BCAAs)increased and gut microbiota disordered in type 2 diabetes mellitus(T2DM).This study aimed to investigate the mechanism of Lactiplantibacillus plantarum strain 84-3(Lp84-3)combined with Staphylococcus aureus bacteriophage on ameliorating T2DM.Here we perform a case-control study and identify that Staphylococcus_phage was inversely correlated with fasting blood glucose(FBG).It revealed that Lp84-3 could inhibit the growth of S.aureus,and Lp84-3 contains BCAAs degradation enzymes in its genome.Furthermore,Lp84-3 alone or combined with S.aureus bacteriophage interventions can improve blood glucose,insulin resistance,triglycerides,interleukin-1β,tumor necrosis factor-α(TNF-α),BCAAs,and acetyllactate synthase(ALS)in db/db mice.Lp84-3 and S.aureus bacteriophage decreased S.aureus,Malacoplasma iowae,and Oscillibacter sp.,and increased some beneficial such as L.plantarum and Muribaculaceae bacterium.Transcriptomic analyses revealed that Lp84-3 and S.aureus bacteriophage activated the PI3K/AKT/GLUT4 signaling pathway and upregulated key genes of Il22,Hgf,Col6a1,Gh,Itga10,Fgf23,and Prl involved in glucose metabolism in hypothalamus.Collectively,Lp84-3 and S.aureus bacteriophage alleviate T2DM by modulating gut microbiota and enhancing glucose metabolism in hypothalamus,supporting its potential use as a promising functional compound microecological agent for alleviating T2DM.展开更多
In the post-antibiotic era,the overuse of antimicrobials has led to a massive increase in antimicrobial resistance,leaving medical doctors few or no treatment options to fight infections caused by superbugs.The use of...In the post-antibiotic era,the overuse of antimicrobials has led to a massive increase in antimicrobial resistance,leaving medical doctors few or no treatment options to fight infections caused by superbugs.The use of bacteriophages is a promising alternative to treat infections,supplementing or possibly even replacing antibiotics.Using phages for therapy is possible,since these bacterial viruses can kill bacteria specifically,causing no harm to the normal flora.However,bacteria have developed a multitude of sophisticated and complex ways to resist infection by phages,including abortive infection and the clustered regularly interspersed short palindromic repeats(CRISPR)/CRISPR-associated(Cas)system.Phages also can evolve and acquire new anti-defense strategies to continue predation.An in-depth exploration of both defense and anti-defense mechanisms would contribute to optimizing phage therapy,while we would also gain novel insights into the microbial world.In this paper,we summarize recent research on bacterial phage resistance and phage anti-defense mechanisms,as well as collaborative win-win systems involving both virus and host.展开更多
The practice of phage therapy,which uses bacterial viruses(phages)to treat bacterial infections,has been around for almost a century.The universal decline in the effectiveness of antibiotics has generated renewed inte...The practice of phage therapy,which uses bacterial viruses(phages)to treat bacterial infections,has been around for almost a century.The universal decline in the effectiveness of antibiotics has generated renewed interest in revisiting this practice.Conventionally,phage therapy relies on the use of naturally-occurring phages to infect and lyse bacteria at the site of infection.Biotechnological advances have further expanded the repertoire of potential phage therapeutics to include novel strategies using bioengineered phages and purified phage lytic proteins.Current research on the use of phages and their lytic proteins against multidrug-resistant bacterial infections,suggests phage therapy has the potential to be used as either an alternative or a supplement to antibiotic treatments.Antibacterial therapies,whether phage-or antibiotic-based,each have relative advantages and disadvantages;accordingly,many considerations must be taken into account when designing novel therapeutic approaches for preventing and treating bacterial infection.Although much about phages and human health is still being discovered,the time to take phage therapy serious again seems to be rapidly approaching.展开更多
In the present medicine world antibiotic resistance is one of the key threats to universal health coverage.Researchers continue to work hard to combat this global health concern.Phage therapy,an age-old practice durin...In the present medicine world antibiotic resistance is one of the key threats to universal health coverage.Researchers continue to work hard to combat this global health concern.Phage therapy,an age-old practice during the early twentieth century,was outshined by the discovery of antibiotics.With the advent of widespread antibiotic resistance,phage therapy has again redeemed itself as a potential alternative owing to its adeptness to target bacteria precisely.Limited side effects,the ability to migrate to different body organs,a distinct mode of action,and proliferation at the infection site,make phages a profitable candidate to replace conventional antibiotics.The progressive outcome of numerous in vitro studies and case reports has validated the clinical efficacy of phage therapy.The bright perspective of using phages to treat bacterial infections has fueled enormous medical research to exploit their potential as therapeutics.The gaps in the information about phages and the lack of consent for clinical trials is major hurdle for consideration of phage therapy.Crafting phage therapy as a reality in medicine requires a coordinated effort from different fraternities.With this review,we aim to emphasize the importance of phage therapy in modern medicine.This review explains their historical journey,basic phage biology,cross-talk with the host immunity,obstacles with phage therapy,and their possible remedies.Comprehensive data on the various significant clinical trials of phage therapy has been presented.We evaluated the efficacy of antibiotics and phage therapy in part and in combination,along with recent progress and future perspectives of phage therapy.展开更多
The emergence of multidrug-resistant bacterial pathogens forced us to consider the phage therapy as one of the possible alternative approaches to treatment. The purpose of this paper is to consider the conditions for ...The emergence of multidrug-resistant bacterial pathogens forced us to consider the phage therapy as one of the possible alternative approaches to treatment. The purpose of this paper is to consider the conditions for the safe, long-term use of phage therapy against various infections caused by Pseudomonas aeruginosa. We describe the selection of the most suitable phages, their most effective combinations and some approaches for the rapid recognition of phages unsuitable for use in therapy. The benefi ts and disadvantages of the various different approaches to the preparation of phage mixtures are considered, together with the specifi c conditions that are required for the safe application of phage therapy in general hospitals and the possibilities for the development of personalized phage therapy.展开更多
Stutzerimonas have been extensively studied due to their remarkable metabolic and physiological diversity.However,research on its phages is currently limited.In this study,we isolated a novel double-stranded DNA(dsDNA...Stutzerimonas have been extensively studied due to their remarkable metabolic and physiological diversity.However,research on its phages is currently limited.In this study,we isolated a novel double-stranded DNA(dsDNA)phage,vB_SstM-PG1,from the marine environment that infects Stutzerimonas stutzeri G1.Its dsDNA genome is 37204 bp long with a G/C content of 64.14%and encodes 54 open reading frames.The phage possesses a tail packaging structure that is different from known Stutzerimonas stutzeri phages and exhibits structural protein characteristics similar to those of temperate phages.In addition,two genes of toxin-antitoxin system,including YdaS_antitoxin and HEPN_SAV_6107,were found in the vB_SstM-PG1 genome and play important roles in regulating host growth and metabolism.With phylogenetic tree and comparative genomic analysis,it has been determined that vB_SstM-PG1 is not closely related to any phages previously identified in the GenBank database.Instead,it has a connection with enigmatic,uncultured viruses.Specifically,the vB_SstM-PG1 virus exhibits an average nucleotide identity of over 70%with six uncultivated viruses identified in the IMG/VR v4 database.This significant finding has resulted in the identification of a novel viral genus known as Metabovirus.展开更多
Acinetobacter baumannii(A.baumannii)poses a serious public health challenge due to its notorious antimicrobial resistance,particularly carbapenem-resistant A.baumannii(CRAB).In this study,we isolated a virulent phage,...Acinetobacter baumannii(A.baumannii)poses a serious public health challenge due to its notorious antimicrobial resistance,particularly carbapenem-resistant A.baumannii(CRAB).In this study,we isolated a virulent phage,named P1068,from medical wastewater capable of lysing CRAB,primarily targeting the K3 capsule type.Basic characterization showed that P1068 infected the A.baumannii ZWAb014 with an optimal MOI of 1,experienced a latent period of 10 min and maintained stability over a temperature range of 4–37C and pH range of 3–10.Phylogenetic and average nucleotide identity analyses indicate that P1068 can be classified as a novel species within the genus Obolenskvirus of the Caudoviricetes class as per the most recent virus classification released by the International Committee on Taxonomy of Viruses(ICTV).Additionally,according to classical morphological classification,P1068 is identified as a T4-like phage(Myoviridae).Interestingly,we found that the tail fiber protein(TFP)of P1068 shares 74%coverage and 88.99%identity with the TFP of a T7-like phage(Podoviridae),AbKT21phiIII(NC_048142.1).This finding suggests that the TFP gene of phages may undergo horizontal transfer across different genera and morphologies.In vitro antimicrobial assays showed that P1068 exhibited antimicrobial activity against A.baumannii in both biofilm and planktonic states.In mouse models of intraperitoneal infection,P1068 phage protected mice from A.baumannii infection and significantly reduced bacterial loads in various tissues such as the brain,blood,lung,spleen,and liver compared to controls.In conclusion,this study demonstrates that phage P1068 might be a potential candidate for the treatment of carbapenem-resistant and biofilmforming A.baumannii infections,and expands the understanding of horizontal transfer of phage TFP genes.展开更多
Hepatitis B virus(HBV) infection is a major global health challenge leading to serious disorders such as cirrhosis and hepatocellular carcinoma. Currently, there exist various diagnostic and therapeutic approaches for...Hepatitis B virus(HBV) infection is a major global health challenge leading to serious disorders such as cirrhosis and hepatocellular carcinoma. Currently, there exist various diagnostic and therapeutic approaches for HBV infection. However, prevalence and hazardous effects of chronic viral infection heighten the need to develop novel methodologies for the detection and treatment of this infection. Bacteriophages, viruses that specifically infect bacterial cells, with a long-established tradition in molecular biology and biotechnology have recently been introduced as novel tools for the prevention, diagnosis and treatment of HBV infection. Bacteriophages, due to tremendous genetic flexibility, represent potential to undergo a huge variety of surface modifications. This property has been the rationale behind introduction of phage display concept. This powerful approach, together with combinatorial chemistry, has shaped the concept of phage display libraries with diverse applications for the detection and therapy of HBV infection. This review aims to offer an insightful overview of the potential of bacteriophages in the development of helpful prophylactic(vaccine design), diagnostic and therapeutic strategies for HBV infection thereby providing new perspec-tives to the growing field of bacteriophage researches directing towards HBV infection.展开更多
Acinetobacter baumannii causes serious infections especially in immunocompromised and/or hospitalized patients.Several A.baumannii strains are multidrug resistant and infect wounds,bones,and the respiratory tract.Curr...Acinetobacter baumannii causes serious infections especially in immunocompromised and/or hospitalized patients.Several A.baumannii strains are multidrug resistant and infect wounds,bones,and the respiratory tract.Current studies are focused on finding new effective agents against A.baumannii.Phage therapy is a promising means to fight this bacterium and many studies on procuring and applying new phages against A.baumannii are currently being conducted.As shown in animal models,phages against multidrug-resistant A.baumannii may control bacterial infections caused by this pathogen and may be a real hope to solve this dangerous health problem.展开更多
Soft rot is an economically significant disease in potato and one of the major threats to sustainable potato production.This study aimed at isolating lytic bacteriophages and evaluating methods for and the efficacy of...Soft rot is an economically significant disease in potato and one of the major threats to sustainable potato production.This study aimed at isolating lytic bacteriophages and evaluating methods for and the efficacy of applying phages to control potato soft rot caused by Pectobacterium carotovorum.Eleven bacteriophages isolated from soil and water samples collected in Wuhan,China,were used to infect P.carotovorum host strains isolated from potato tubers showing soft rot symptoms in Nakuru county,Kenya.The efficacy of the phages in controlling soft rot disease was evaluated by applying individual phage strains or a phage cocktail on potato slices and tubers at different time points before or after inoculation with a P.carotovorum strain.The phages could lyse 20 strains of P.carotovorum,but not Pseudomonas fluorescens control strains.Among the 11 phages,Pectobacterium phage Wc5r,interestingly showed cross-activity against Pectobacterium atrosepticum and two phage-resistant P.carotovorum strains.Potato slice assays showed that the phage concentration and timing of application are crucial factors for effective soft rot control.Phage cocktail applied at a concentration of 1×10^9 plaque-forming units per milliliter before or within an hour after bacterial inoculation on potato slices,resulted in>90%reduction of soft rot symptoms.This study provides a basis for the development and application of phages to reduce the impact of potato soft rot disease.展开更多
The year 2015 marks 100 years since Dr.Frederick Twort discovered the"filterable lytic factor",which was later independently discovered and named "bacteriophage" by Dr.Felix d’Herelle.On this memo...The year 2015 marks 100 years since Dr.Frederick Twort discovered the"filterable lytic factor",which was later independently discovered and named "bacteriophage" by Dr.Felix d’Herelle.On this memorable centennial,it is exciting to see a special issue published by Virologica Sinica on Phages and Therapy.In this issue,readers will not only fi nd that bacteriophage research is a展开更多
There are many recent studies regarding the efficacy of bacteriophage-related lytic enzymes: the enzymes of ‘bacteria-eaters' or viruses that infect bacteria. By degrading the cell wall of the targeted bacteria, ...There are many recent studies regarding the efficacy of bacteriophage-related lytic enzymes: the enzymes of ‘bacteria-eaters' or viruses that infect bacteria. By degrading the cell wall of the targeted bacteria, these lytic enzymes have been shown to efficiently lyse Gram-positive bacteria without affecting normal flora and non-related bacteria. Recent studies have suggested approaches for lysing Gram-negative bacteria as well(Briersa Y, et al., 2014). These enzymes include: phage-lysozyme, endolysin, lysozyme, lysin, phage lysin, phage lytic enzymes, phageassociated enzymes, enzybiotics, muralysin, muramidase, virolysin and designations such as Ply, PAE and others. Bacteriophages are viruses that kill bacteria, do not contribute to antimicrobial resistance, are easy to develop, inexpensive to manufacture and safe for humans, animals and the environment. The current focus on lytic enzymes has been on their use as anti-infectives in humans and more recently in agricultural research models. The initial translational application of lytic enzymes, however, was not associated with treating or preventing a specifi c disease but rather as an extraction method to be incorporated in a rapid bacterial detection assay(Bernstein D, 1997).The current review traces the translational history of phage lytic enzymes–from their initial discovery in 1986 for the rapid detection of group A streptococcus in clinical specimens to evolving applications in the detection and prevention of disease in humans and in agriculture.展开更多
In recent years, the development of antibiotic resistant bacteria has become a global concern which has prompted research into the development of alternative disease control strategies for the swine industry. Bacterio...In recent years, the development of antibiotic resistant bacteria has become a global concern which has prompted research into the development of alternative disease control strategies for the swine industry. Bacteriophages （viruses that infect bacteria） offer the prospect of a sustainable alternative approach against bacterial pathogens with the flexibility of being applied therapeutically or for biological control purposes. This paper reviews the use of phages as an antimicrobial strategy for controlling critical pathogens including Salmonella and Eschefich[a coli with an emphasis on the application of phages for improving performance and nutrient digestibility in swine operations as well as in controlling zoonotic human diseases by reducing the bacterial load spread from pork products to humans through the meat,展开更多
基金supported by the Nanjing Infectious Disease Clinical Medical Center,Innovation center for infectious disease of Jiangsu Province(NO.CXZX202232)the Leading Talent Project of Jiangsu Province Traditional Chinese Medicine(NO.SLJ0216)+4 种基金the Nanjing Health science and Technology Development Special fund Project(NO.YKK20102)the General Program of Jiangsu Commission of Health(NO.M2021088)the Nanjing Health science and Technology Development General Project(NO.YKK21121)the 2023 Nanjing Second Hospital Talent Support Project Grant(RCZD23003)the Jiangsu Province Postgraduate Research and Practice Innovation Program(KYCX24_2176).
文摘The treatment of Acinetobacter baumannii(A.baumannii)poses significant clinical challenges due to its multidrug/pan-drug resistance.In this study,we isolated a broad-spectrum lytic A.baumannii phage,named P425,from medical wastewater,targeting nine multidrug-resistant A.baumannii(MDRAB)with diverse capsular types.Biological characterization revealed that P425 maintains activity at pH range of 3–12 and temperature range of 4–50℃.It resists UV irradiation for 20 minutes,and had an optimal multiplicity of infection(OMOI)is 0.00001.The adsorption kinetics showed that P425 achieves>90%within 10 minutes of incubation,and the one-step growth curve indicated a 10-min latent period,with a burst size of 184 PFU/cell.The genome sequencing results indicated that it harbors a double-stranded DNA genome of 40,583 bp with a GC content of 39.39%.Intergenomic similarity analysis classified it as a novel species within the Friunavirus genus,while electron microscopy results showed that it belongs to the Podoviridae family.Notably,P425 exhibits potent 24-h in vitro inhibitory activity against MDRAB,and demonstrates synergistic effect at an MOI of 0.001 when combined with five classes of antibiotics targeting distinct antimicrobial mechanisms.Safety evaluations confirmed the absence of cytotoxicity,hemolytic activity,or systemic toxicity both in vitro and in vivo.In mouse infection models,P425 can significantly improve the survival rates of mice infected with Ab25(ST1791/KL101).When co-administered with levofloxacin,it achieved 100%protection against mortality and promoted immune recovery.Collectively,P425 is a prospective lytic phage that could offer novel strategies for combating MDRAB infections.
文摘Staphylococcus aureus (S. aureus) is a bacterial pathogen for humans and animals. These bacteria can resist against many antibiotics and this resistance constitute an alarming worldwide human health threat due to the morbidity and mortality. Phage therapy is one of the alternative treatments. The aim of this study was to isolate and characterize lytic phages of S. aureus from different wastewater sources in Bobo-Dioulasso, Burkina Faso. Eight strains of S. aureus were isolated from different clinical samples and were used to isolate phages. The isolation and host range of phages were done by the spot test. Phages were purified by the double-layer method. Similar phages after the determination of the host range were characterized using restriction enzymes. A total of 27 phages were obtained after isolation and purification. Nine of the 27 isolates reported a broad host range (≥67%). The results of enzymatic digestion allowed to consider that all phage isolates that presented the same host range and the same genetic fingerprint are the same phage strain;whereas phages that presented the same host range and different genetic fingerprints are different phage strains. Thus, a total of 15 distinct phages isolates specific to S. aureus were characterized. This study highlighted the abundance and lytic capacity of phages isolated from wastewater from Bobo-Dioulasso’s environment against clinical strains of S. aureus. The lytic capacity of these Staphyphages could be an effective alternative tool to combat bacteria multi-resistance.
基金supported by the National Natural Science Foundation of China(Nos.52091545 and 51978645).
文摘The objective of this study is to quantitatively reveal the main genetic carrier of antibiotic resistance genes(ARGs)for blocking their environmental dissemination.The distribution of ARGs in chromosomes,plasmids,and phages for understanding their respective contributions to the development of antimicrobial resistance in aerobic biofilm consortium under increasing stresses of oxytetracycline,streptomycin,and tigecyclinewere revealed based on metagenomics analysis.Results showed that the plasmids harbored 49.2%-83.9%of resistomes,which was higher(p<0.001)than chromosomes(2.0%-35.6%),and no ARGs were detected in phage contigs under the strict alignment standard of over 80%identity used in this study.Plasmids and chromosomes tended to encode different types of ARGs,whose abundances all increased with the hike of antibiotic concentrations,and the variety of ARGs encoded by plasmids(14 types and 64 subtypes)was higher than that(11 types and 27 subtypes)of chromosomes.The dosing of the three antibiotics facilitated the transposition and recombination of ARGs on plasmids,mediated by transposable and integrable transfer elements,which increased the co-occurrence of associated and unassociated ARGs.The results quantitatively proved that plasmids dominate the proliferation of ARGs in aerobic biofilm driven by antibiotic selection,which should be a key target for blocking ARG dissemination.
基金the National Natural Science Foundation of China(Nos.42188102,42120104006,41976117,42176111)the Fundamental Research Funds for the Central Universities(Nos.202172002,201812002)the funding from Andrew Mc Minn。
文摘Pseudoalteromonas is a group of marine bacteria widespread in diverse marine sediments,producing a wide range of bioactive compounds.However,only a limited number of Pseudoalteromonas phages have been isolated and studied.In this study,a novel lytic Pseudoalteromonas phage,denoted as vB_PalP_Y7,was isolated from sewage samples collected at the Seafood Market in Qingdao,China.vB_PalP_Y7 remained stable across a wide range of temperatures(-20–50℃)and a wide pH range(3–12).The vB_PalP_Y7 phage harbors a linear double-stranded DNA molecule of 57699 base pairs(bp)with a G+C content of 45.90%.Furthermore,it is predicted to contain 58 open reading frames(ORFs).Phylogenetic analysis and protein network relationship analysis revealed low similarity between vB_PalP_Y7 and viruses in the ICTV and IMG/VR4 database,suggesting that vB_PalP_Y7 may be a potential new genus,Miuvirus.This study contributed valuable insights to comprehend the relationship between Pseudoalteromonas phages and their host organisms.
基金supported by grants from the National Program on Key Research Project of China[2022YFD1800800,2021YFD1800300]the Yingzi Tech&Huazhong Agricultural University Intelligent Research Institute of Food Health[No.IRIFH202209,No.IRIFH202301]The National Program on Key Research Project of China,2022YFD1800800,Ping Qian,2021YFD1800300,Ping Qian,The Yingzi Tech&Huazhong Agricultural University Intelligent Research Institute of Food Health,IRIFH202209,Ping Qian,IRIFH202301,Ping Qian.
文摘Enterotoxigenic E.coli is one of the bacterial pathogens contributing to the global resistance crisis in public health and animal husbandry.The problem of antibiotic resistance is becoming more and more serious,and phage is con-sidered one of the potential alternatives to antibiotics that could be utilized to treat bacterial infections.Our study isolated and identified a lytic phage PGX1 against multidrug-resistant enterotoxigenic E.coli EC6 strain from sew-age.The phage lysis profile revealed that PGX1 exhibited a lytic effect on multidrug-resistant enterotoxigenic E.coli strains of serotype O60.Through phage whole genome sequencing and bioinformatics analysis,PGX1 was found to be the class Caudoviricetes,family Autographiviridae,genus Teseptimavirus.The length of the PGX1 genome is about 37,009 bp,containing 54 open reading frames(ORFs).Notably,phage PGX1 lacks any lysogenic-related genes or virulence genes.Furthermore,phage PGX1 demonstrates strong adaptability,tolerance,and stability in various pH(pH4-10)and temperatures(4–40°C).The in vivo and in vitro tests demonstrated that phage PGX1 significantly removes and inhibits the formation of multidrug-resistant EC6 biofilm and effectively controls the Galleria mel-lonella larvae and enterotoxigenic E.coli EC6 during mice infection.In conclusion,the above findings demonstrated that phage PGX1 may be a novel antimicrobial agent to control multidrug-resistant E.coli infections.
基金supported by research grants from the Guangdong Province Basic and Applied Basic Research Fund Project(2022A1515110447)Open Fund Project of the State Key Laboratory of Applied Microbiology in South China(SKLAM006-2022)+1 种基金74th batch of general funding from the China Postdoctoral Science Foundation(2023M740774)Guangdong Provincial People’s Hospital,Postdoctoral Research Launch Fund(BY012022017)。
文摘Epidemiological studies have indicated that branched-chain amino acids(BCAAs)increased and gut microbiota disordered in type 2 diabetes mellitus(T2DM).This study aimed to investigate the mechanism of Lactiplantibacillus plantarum strain 84-3(Lp84-3)combined with Staphylococcus aureus bacteriophage on ameliorating T2DM.Here we perform a case-control study and identify that Staphylococcus_phage was inversely correlated with fasting blood glucose(FBG).It revealed that Lp84-3 could inhibit the growth of S.aureus,and Lp84-3 contains BCAAs degradation enzymes in its genome.Furthermore,Lp84-3 alone or combined with S.aureus bacteriophage interventions can improve blood glucose,insulin resistance,triglycerides,interleukin-1β,tumor necrosis factor-α(TNF-α),BCAAs,and acetyllactate synthase(ALS)in db/db mice.Lp84-3 and S.aureus bacteriophage decreased S.aureus,Malacoplasma iowae,and Oscillibacter sp.,and increased some beneficial such as L.plantarum and Muribaculaceae bacterium.Transcriptomic analyses revealed that Lp84-3 and S.aureus bacteriophage activated the PI3K/AKT/GLUT4 signaling pathway and upregulated key genes of Il22,Hgf,Col6a1,Gh,Itga10,Fgf23,and Prl involved in glucose metabolism in hypothalamus.Collectively,Lp84-3 and S.aureus bacteriophage alleviate T2DM by modulating gut microbiota and enhancing glucose metabolism in hypothalamus,supporting its potential use as a promising functional compound microecological agent for alleviating T2DM.
基金This work was supported by the Western Medicine Program of the Zhejiang Provincial Health Commission(No.2024KY592)the Fundamental Research Funds for Central Universities of the Central South University(No.2-2050205-19-361),China.
文摘In the post-antibiotic era,the overuse of antimicrobials has led to a massive increase in antimicrobial resistance,leaving medical doctors few or no treatment options to fight infections caused by superbugs.The use of bacteriophages is a promising alternative to treat infections,supplementing or possibly even replacing antibiotics.Using phages for therapy is possible,since these bacterial viruses can kill bacteria specifically,causing no harm to the normal flora.However,bacteria have developed a multitude of sophisticated and complex ways to resist infection by phages,including abortive infection and the clustered regularly interspersed short palindromic repeats(CRISPR)/CRISPR-associated(Cas)system.Phages also can evolve and acquire new anti-defense strategies to continue predation.An in-depth exploration of both defense and anti-defense mechanisms would contribute to optimizing phage therapy,while we would also gain novel insights into the microbial world.In this paper,we summarize recent research on bacterial phage resistance and phage anti-defense mechanisms,as well as collaborative win-win systems involving both virus and host.
基金Supported by Winkler Bacterial Overgrowth Research Fund(in part)
文摘The practice of phage therapy,which uses bacterial viruses(phages)to treat bacterial infections,has been around for almost a century.The universal decline in the effectiveness of antibiotics has generated renewed interest in revisiting this practice.Conventionally,phage therapy relies on the use of naturally-occurring phages to infect and lyse bacteria at the site of infection.Biotechnological advances have further expanded the repertoire of potential phage therapeutics to include novel strategies using bioengineered phages and purified phage lytic proteins.Current research on the use of phages and their lytic proteins against multidrug-resistant bacterial infections,suggests phage therapy has the potential to be used as either an alternative or a supplement to antibiotic treatments.Antibacterial therapies,whether phage-or antibiotic-based,each have relative advantages and disadvantages;accordingly,many considerations must be taken into account when designing novel therapeutic approaches for preventing and treating bacterial infection.Although much about phages and human health is still being discovered,the time to take phage therapy serious again seems to be rapidly approaching.
文摘In the present medicine world antibiotic resistance is one of the key threats to universal health coverage.Researchers continue to work hard to combat this global health concern.Phage therapy,an age-old practice during the early twentieth century,was outshined by the discovery of antibiotics.With the advent of widespread antibiotic resistance,phage therapy has again redeemed itself as a potential alternative owing to its adeptness to target bacteria precisely.Limited side effects,the ability to migrate to different body organs,a distinct mode of action,and proliferation at the infection site,make phages a profitable candidate to replace conventional antibiotics.The progressive outcome of numerous in vitro studies and case reports has validated the clinical efficacy of phage therapy.The bright perspective of using phages to treat bacterial infections has fueled enormous medical research to exploit their potential as therapeutics.The gaps in the information about phages and the lack of consent for clinical trials is major hurdle for consideration of phage therapy.Crafting phage therapy as a reality in medicine requires a coordinated effort from different fraternities.With this review,we aim to emphasize the importance of phage therapy in modern medicine.This review explains their historical journey,basic phage biology,cross-talk with the host immunity,obstacles with phage therapy,and their possible remedies.Comprehensive data on the various significant clinical trials of phage therapy has been presented.We evaluated the efficacy of antibiotics and phage therapy in part and in combination,along with recent progress and future perspectives of phage therapy.
文摘The emergence of multidrug-resistant bacterial pathogens forced us to consider the phage therapy as one of the possible alternative approaches to treatment. The purpose of this paper is to consider the conditions for the safe, long-term use of phage therapy against various infections caused by Pseudomonas aeruginosa. We describe the selection of the most suitable phages, their most effective combinations and some approaches for the rapid recognition of phages unsuitable for use in therapy. The benefi ts and disadvantages of the various different approaches to the preparation of phage mixtures are considered, together with the specifi c conditions that are required for the safe application of phage therapy in general hospitals and the possibilities for the development of personalized phage therapy.
基金supported by the National Natural Science Foundation of China (Nos.42188102,42120104006,41976117,42176111 and 42306111)the Fundamental Research Funds for the Central Universities (No.201812002 and Andrew McMinn)。
文摘Stutzerimonas have been extensively studied due to their remarkable metabolic and physiological diversity.However,research on its phages is currently limited.In this study,we isolated a novel double-stranded DNA(dsDNA)phage,vB_SstM-PG1,from the marine environment that infects Stutzerimonas stutzeri G1.Its dsDNA genome is 37204 bp long with a G/C content of 64.14%and encodes 54 open reading frames.The phage possesses a tail packaging structure that is different from known Stutzerimonas stutzeri phages and exhibits structural protein characteristics similar to those of temperate phages.In addition,two genes of toxin-antitoxin system,including YdaS_antitoxin and HEPN_SAV_6107,were found in the vB_SstM-PG1 genome and play important roles in regulating host growth and metabolism.With phylogenetic tree and comparative genomic analysis,it has been determined that vB_SstM-PG1 is not closely related to any phages previously identified in the GenBank database.Instead,it has a connection with enigmatic,uncultured viruses.Specifically,the vB_SstM-PG1 virus exhibits an average nucleotide identity of over 70%with six uncultivated viruses identified in the IMG/VR v4 database.This significant finding has resulted in the identification of a novel viral genus known as Metabovirus.
基金supported by a grant from the NHC Key laboratory of Enteric Pathogenic Microbiology(Jiangsu Provincial Center for Disease Control and Prevention,EM202303)Guizhou Province Science and Technology Plan Project(Grant No.QKH[2023]008)+3 种基金the Science Foundation of Jiangsu Province Health Department(ZDB2020014)National Natural Science Foundation of China(82002108)Science and Technology Program of Suzhou(SKYD2023050)Suzhou Municipal Health Commission(KJXW2023061).
文摘Acinetobacter baumannii(A.baumannii)poses a serious public health challenge due to its notorious antimicrobial resistance,particularly carbapenem-resistant A.baumannii(CRAB).In this study,we isolated a virulent phage,named P1068,from medical wastewater capable of lysing CRAB,primarily targeting the K3 capsule type.Basic characterization showed that P1068 infected the A.baumannii ZWAb014 with an optimal MOI of 1,experienced a latent period of 10 min and maintained stability over a temperature range of 4–37C and pH range of 3–10.Phylogenetic and average nucleotide identity analyses indicate that P1068 can be classified as a novel species within the genus Obolenskvirus of the Caudoviricetes class as per the most recent virus classification released by the International Committee on Taxonomy of Viruses(ICTV).Additionally,according to classical morphological classification,P1068 is identified as a T4-like phage(Myoviridae).Interestingly,we found that the tail fiber protein(TFP)of P1068 shares 74%coverage and 88.99%identity with the TFP of a T7-like phage(Podoviridae),AbKT21phiIII(NC_048142.1).This finding suggests that the TFP gene of phages may undergo horizontal transfer across different genera and morphologies.In vitro antimicrobial assays showed that P1068 exhibited antimicrobial activity against A.baumannii in both biofilm and planktonic states.In mouse models of intraperitoneal infection,P1068 phage protected mice from A.baumannii infection and significantly reduced bacterial loads in various tissues such as the brain,blood,lung,spleen,and liver compared to controls.In conclusion,this study demonstrates that phage P1068 might be a potential candidate for the treatment of carbapenem-resistant and biofilmforming A.baumannii infections,and expands the understanding of horizontal transfer of phage TFP genes.
文摘Hepatitis B virus(HBV) infection is a major global health challenge leading to serious disorders such as cirrhosis and hepatocellular carcinoma. Currently, there exist various diagnostic and therapeutic approaches for HBV infection. However, prevalence and hazardous effects of chronic viral infection heighten the need to develop novel methodologies for the detection and treatment of this infection. Bacteriophages, viruses that specifically infect bacterial cells, with a long-established tradition in molecular biology and biotechnology have recently been introduced as novel tools for the prevention, diagnosis and treatment of HBV infection. Bacteriophages, due to tremendous genetic flexibility, represent potential to undergo a huge variety of surface modifications. This property has been the rationale behind introduction of phage display concept. This powerful approach, together with combinatorial chemistry, has shaped the concept of phage display libraries with diverse applications for the detection and therapy of HBV infection. This review aims to offer an insightful overview of the potential of bacteriophages in the development of helpful prophylactic(vaccine design), diagnostic and therapeutic strategies for HBV infection thereby providing new perspec-tives to the growing field of bacteriophage researches directing towards HBV infection.
基金supported by the statutory funds from the Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences
文摘Acinetobacter baumannii causes serious infections especially in immunocompromised and/or hospitalized patients.Several A.baumannii strains are multidrug resistant and infect wounds,bones,and the respiratory tract.Current studies are focused on finding new effective agents against A.baumannii.Phage therapy is a promising means to fight this bacterium and many studies on procuring and applying new phages against A.baumannii are currently being conducted.As shown in animal models,phages against multidrug-resistant A.baumannii may control bacterial infections caused by this pathogen and may be a real hope to solve this dangerous health problem.
基金supported financially by the Sino-Africa Joint Research Centre (SAJC201605)the Chinese Academy of Sciences (ZDRW-ZS-2016-4)
文摘Soft rot is an economically significant disease in potato and one of the major threats to sustainable potato production.This study aimed at isolating lytic bacteriophages and evaluating methods for and the efficacy of applying phages to control potato soft rot caused by Pectobacterium carotovorum.Eleven bacteriophages isolated from soil and water samples collected in Wuhan,China,were used to infect P.carotovorum host strains isolated from potato tubers showing soft rot symptoms in Nakuru county,Kenya.The efficacy of the phages in controlling soft rot disease was evaluated by applying individual phage strains or a phage cocktail on potato slices and tubers at different time points before or after inoculation with a P.carotovorum strain.The phages could lyse 20 strains of P.carotovorum,but not Pseudomonas fluorescens control strains.Among the 11 phages,Pectobacterium phage Wc5r,interestingly showed cross-activity against Pectobacterium atrosepticum and two phage-resistant P.carotovorum strains.Potato slice assays showed that the phage concentration and timing of application are crucial factors for effective soft rot control.Phage cocktail applied at a concentration of 1×10^9 plaque-forming units per milliliter before or within an hour after bacterial inoculation on potato slices,resulted in>90%reduction of soft rot symptoms.This study provides a basis for the development and application of phages to reduce the impact of potato soft rot disease.
基金supported by the Basic Research Program of the Ministry of Science and Technology of China(2012CB721102)the Chinese Academy of Sciences(grant No:KJZD-EW-L02)the Key Laboratory on Emerging Infectious Diseases and Biosafety in Wuhan
文摘The year 2015 marks 100 years since Dr.Frederick Twort discovered the"filterable lytic factor",which was later independently discovered and named "bacteriophage" by Dr.Felix d’Herelle.On this memorable centennial,it is exciting to see a special issue published by Virologica Sinica on Phages and Therapy.In this issue,readers will not only fi nd that bacteriophage research is a
文摘There are many recent studies regarding the efficacy of bacteriophage-related lytic enzymes: the enzymes of ‘bacteria-eaters' or viruses that infect bacteria. By degrading the cell wall of the targeted bacteria, these lytic enzymes have been shown to efficiently lyse Gram-positive bacteria without affecting normal flora and non-related bacteria. Recent studies have suggested approaches for lysing Gram-negative bacteria as well(Briersa Y, et al., 2014). These enzymes include: phage-lysozyme, endolysin, lysozyme, lysin, phage lysin, phage lytic enzymes, phageassociated enzymes, enzybiotics, muralysin, muramidase, virolysin and designations such as Ply, PAE and others. Bacteriophages are viruses that kill bacteria, do not contribute to antimicrobial resistance, are easy to develop, inexpensive to manufacture and safe for humans, animals and the environment. The current focus on lytic enzymes has been on their use as anti-infectives in humans and more recently in agricultural research models. The initial translational application of lytic enzymes, however, was not associated with treating or preventing a specifi c disease but rather as an extraction method to be incorporated in a rapid bacterial detection assay(Bernstein D, 1997).The current review traces the translational history of phage lytic enzymes–from their initial discovery in 1986 for the rapid detection of group A streptococcus in clinical specimens to evolving applications in the detection and prevention of disease in humans and in agriculture.
基金the National Public Science and Technology Research Funds Projects of Ocean(Grant No.201405003-3)
文摘In recent years, the development of antibiotic resistant bacteria has become a global concern which has prompted research into the development of alternative disease control strategies for the swine industry. Bacteriophages （viruses that infect bacteria） offer the prospect of a sustainable alternative approach against bacterial pathogens with the flexibility of being applied therapeutically or for biological control purposes. This paper reviews the use of phages as an antimicrobial strategy for controlling critical pathogens including Salmonella and Eschefich[a coli with an emphasis on the application of phages for improving performance and nutrient digestibility in swine operations as well as in controlling zoonotic human diseases by reducing the bacterial load spread from pork products to humans through the meat,
