Fungi are an integral part of the earth's biosphere.They are broadly distributed in all continents and ecosystems and play a diversity of roles.Here,I review our current understanding of fungal threats to humans a...Fungi are an integral part of the earth's biosphere.They are broadly distributed in all continents and ecosystems and play a diversity of roles.Here,I review our current understanding of fungal threats to humans and describe the major factors that contribute to various threats.Among the 140,000 or so known species out of the estimated six million fungal species on Earth,about 10%directly or indirectly threaten human health and welfare.Major threats include mushroom poisoning,fungal allergies,infections of crop plants,food contamination by mycotoxins,and mycoses in humans.A growing number of factors have been identified to impact various fungal threats,including human demographics,crop distributions,anthropogenic activities,pathogen dispersals,global climate change,and/or the applications of antifungal drugs and agricultural fungicides.However,while models have been developed for analyzing various processes of individual threats and threat managements,current data are primarily descriptive and incomplete,and there are significant obstacles to integration of the diverse factors into accurate quantitative assessments of fungal threats.With increasing technological advances and concerted efforts to track the spatial and temporal data on climate and environmental variables;mycotoxins in the feed and food supply chains;fungal population dynamics in crop fields,human and animal populations,and the environment;human population demographics;and the prevalence and severities of fungal allergies and diseases,our ability to accurately assess fungal threats will improve.Such improvements should help us develop holistic strategies to manage fungal threats in the future.展开更多
Impact Statement We present a method of mapping data from publicly available genomics and publication resources to the Resource Description Framework(RDF)and implement a server to publish linked open data(LOD).As one ...Impact Statement We present a method of mapping data from publicly available genomics and publication resources to the Resource Description Framework(RDF)and implement a server to publish linked open data(LOD).As one of the largest and most comprehensive semantic databases about coronaviruses,the resulted gcCov database demonstrates the capability of using data in the LOD framework to promote correlations between genotypes and phenotypes.These correlations will be helpful for future research on fundamental viral mechanisms and drug and vaccine designs.展开更多
Lignin degradation is a major process in the global carbon cycle across both terrestrial and marine ecosystems.Bathyarchaeia,which are among the most abundant microorganisms in marine sediment,have been proposed to me...Lignin degradation is a major process in the global carbon cycle across both terrestrial and marine ecosystems.Bathyarchaeia,which are among the most abundant microorganisms in marine sediment,have been proposed to mediate anaerobic lignin degradation.However,the mechanism of bathyarchaeial lignin degradation remains unclear.Here,we report an enrichment culture of Bathy-archaeia,named Candidatus Baizosediminiarchaeum ligniniphilus DL1YTT001(Ca.B.ligniniphilus),from coastal sediments that can grow with lignin as the sole organic carbon source under mesophilic anoxic conditions.Ca.B.ligniniphilus possesses and highly expresses novel methyltransferase 1(MT1,mtgB)for transferring methoxyl groups from lignin monomers to cob(I)alamin.MtgBs have no homology with known microbial methyltransferases and are present only in bathyarchaeial lineages.Heterologous expression of the mtgB gene confirmed O-demethylation activity.The mtgB genes were identified in metagenomic data sets from a wide range of coastal sediments,and they were highly expressed in coastal sediments from the East China Sea.These findings suggest that Bathyarchaeia,capable of O-demethylation via their novel and specific methyltransferases,are ubiquitous in coastal sediments.展开更多
Atherosclerosis is a chronic inflammatory metabolic disease with a complex pathogenesis.However,the exact details of its pathogenesis are still unclear,which limits effective clinical treatment of atherosclerosis.Rece...Atherosclerosis is a chronic inflammatory metabolic disease with a complex pathogenesis.However,the exact details of its pathogenesis are still unclear,which limits effective clinical treatment of atherosclerosis.Recently,multiple studies have demonstrated that the gut microbiota plays a pivotal role in the onset and progression of atherosclerosis.This review discusses possible treatments for atherosclerosis using the gut microbiome as an intervention target and summarizes the role of the gut microbiome and its metabolites in the development of atherosclerosis.New strategies for the treatment of atherosclerosis are needed.This review provides clues for further research on the mechanisms of the relationship between the gut microbiota and atherosclerosis.展开更多
Despite the fast progress in our understanding of the complex functions of gut microbiota,it is still challenging to directly investigate the in vivo microbial activities and processes on an individual cell basis.To g...Despite the fast progress in our understanding of the complex functions of gut microbiota,it is still challenging to directly investigate the in vivo microbial activities and processes on an individual cell basis.To gain knowledge of the indigenous growth/division patterns of the diverse mouse gut bacteria with a relatively high throughput,here,we propose an integrative strategy,which combines the use of fluorescent probe labeling,confocal imaging with single‐cell sorting,and sequencing.Mouse gut bacteria sequentially labeled by two fluorescent D‐amino acid probes in vivo were first imaged by confocal microscopy to visualize their growth patterns,which can be unveiled by the distribution of the two fluorescence signals on each bacterium.Bacterial cells of interest on the imaging slide were then sorted using a laser ejection equipment,and the collected cells were then sequenced individually to identify their taxa.Our strategy allows integrated acquirement of the growth pattern knowledge of a variety of gut bacteria and their genomic information on a single‐cell basis,which should also have great potential in studying many other complex bacterial systems.展开更多
Impact statement.Evolutionary training of phages can help to counter bacterial resistance evolution.Here,we address whether metapopulation processes can enhance the evolution of phage infectivity.Our experiment with a...Impact statement.Evolutionary training of phages can help to counter bacterial resistance evolution.Here,we address whether metapopulation processes can enhance the evolution of phage infectivity.Our experiment with a model bacterium-phage system supported a prediction of long-term fluctuating selection dynamics.Specifically,metapopulations of several small habitats showed greater total infectivity ranges by supporting more diverse phages,compared with single large populations.展开更多
The human gut is home to nearly 100 trillion microbes1,which constitute the human gut microecological system.The microbiota–gut–brain(MGB)axis is a two‐way communication pathway between gut microbiota and the brain...The human gut is home to nearly 100 trillion microbes1,which constitute the human gut microecological system.The microbiota–gut–brain(MGB)axis is a two‐way communication pathway between gut microbiota and the brain through the immune system,metabolism,and the enteric nervous system.An increasing amount of clinical evidence indicates that abnormal MBG axis communication caused by intestinal ecosystem imbalance can affect the development of many neurological diseases,such as Parkinson's disease,Alzheimer's disease,and autism spectrum disorder(ASD)2.展开更多
Photosynthesis has been the cornerstone of solar energy conversion on Earth for billions of years,crucial for sustaining the biosphere and maintaining the carbon and water cycles.However,with the rise of industrial ci...Photosynthesis has been the cornerstone of solar energy conversion on Earth for billions of years,crucial for sustaining the biosphere and maintaining the carbon and water cycles.However,with the rise of industrial civilization,natural photosynthesis alone has become insufficient to meet growing energy and product demands1,leading to extensive fossil fuel use,environmental pollution,and energy crises.In response,scientists have sought to enhance natural photosynthesis through genetic engineering and synthetic biology2,or to develop alternative solar conversion methods using advanced materials science3.展开更多
As the largest organ of the body,the skin acts as a barrier to prevent diseases and harbors a variety of beneficial bacteria.Furthermore,the skin bacterial microbiota plays a vital role in health and disease.Disruptio...As the largest organ of the body,the skin acts as a barrier to prevent diseases and harbors a variety of beneficial bacteria.Furthermore,the skin bacterial microbiota plays a vital role in health and disease.Disruption of the barrier or an imbalance between symbionts and pathogens can lead to skin disorders or even systemic diseases.In this review,we first provide an overview of research on skin bacterial microbiota and human health,including the composition of skin bacteria in a healthy state,as well as skin bacterial microbiota educating the immune system and preventing the invasion of pathogens.We then discuss the diseases that result from skin microbial dysbiosis,including atopic dermatitis,common acne,chronic wounds,psoriasis,viral transmission,cutaneous lupus,cutaneous lymphoma,and hidradenitis suppurativa.Finally,we highlight the progress that utilizes skin microorganisms for disease therapeutics,such as bacteriotherapy and skin microbiome transplantation.A deeper knowledge of the interaction between human health and disease and the homeostasis of the skin bacterial microbiota will lead to new insights and strategies for exploiting skin bacteria as a novel therapeutic target.展开更多
Marine microbiomes are integral to the functioning of a healthy ocean and have the potential to be key contributors toward an all-Atlantic sustainable blue bioeconomy(Figure 1).New compounds may be developed based on ...Marine microbiomes are integral to the functioning of a healthy ocean and have the potential to be key contributors toward an all-Atlantic sustainable blue bioeconomy(Figure 1).New compounds may be developed based on these microbiomes.The Atlantic Ocean is a biodiversity hotspot.The All-Atlantic Ocean Research and Innovation Alliance(AAORIA)Declaration,signed in 2022 in Washington,DC,is a promising mechanism to move forward marine microbiome science,technology,and innovation.展开更多
Broad-spectrum antibacterial drugs often lack specificity,leading to indiscriminate bactericidal activity,which can disrupt the normal microbial balance of the host flora and cause unnecessary cytotoxicity during syst...Broad-spectrum antibacterial drugs often lack specificity,leading to indiscriminate bactericidal activity,which can disrupt the normal microbial balance of the host flora and cause unnecessary cytotoxicity during systemic administration.In this study,we constructed a specifically targeted antimicrobial peptide against Staphylococcus aureus by introducing a phage-displayed peptide onto a broad-spectrum antimicrobial peptide and explored its structure–function relationship through one-factor modification.SFK2 obtained by screening based on the selectivity index and the targeting index showed specific killing ability against S.aureus.Moreover,SFK2 showed excellent biocompatibility in mice and piglet,and demonstrated significant therapeutic efficacy against S.aureus infection.In conclusion,our screening of phage-derived heptapeptides effectively enhances the specific bactericidal ability of the antimicrobial peptides against S.aureus,providing a theoretical basis for developing targeted antimicrobial peptides.展开更多
Sulfate-reducing microorganisms extensively contribute to the corrosion of ferrous metal infrastructure.There is substantial debate over their corrosion mechanisms.We investigated Fe^(0) corrosion with Desulfovibrio v...Sulfate-reducing microorganisms extensively contribute to the corrosion of ferrous metal infrastructure.There is substantial debate over their corrosion mechanisms.We investigated Fe^(0) corrosion with Desulfovibrio vulgaris,the sulfate reducer most often employed in corrosion studies.Cultures were grown with both lactate and Fe^(0) as potential electron donors to replicate the common environmental condition in which organic substrates help fuel the growth of corrosive microbes.Fe^(0) was corroded in cultures of a D.vulgaris hydrogenase-deficient mutant with the 1:1 correspondence between Fe^(0) loss and H_(2) accumulation expected for Fe^(0) oxidation coupled to H+reduction to H_(2).This result and the extent of sulfate reduction indicated that D.vulgaris was not capable of direct Fe^(0)-to-microbe electron transfer even though it was provided with a supplementary energy source in the presence of abundant ferrous sulfide.Corrosion in the hydrogenase-deficient mutant cultures was greater than in sterile controls,demonstrating that H_(2) removal was not necessary for the enhanced corrosion observed in the presence of microbes.The parental H_(2)-consuming strain corroded more Fe^(0) than the mutant strain,which could be attributed to H_(2) oxidation coupled to sulfate reduction,producing sulfide that further stimulated Fe^(0) oxidation.The results suggest that H_(2) consumption is not necessary for microbially enhanced corrosion,but H_(2) oxidation can indirectly promote corrosion by increasing sulfide generation from sulfate reduction.The finding that D.vulgaris was incapable of direct electron uptake from Fe^(0) reaffirms that direct metal-to-microbe electron transfer has yet to be rigorously described in sulfate-reducing microbes.展开更多
Identification,sorting,and sequencing of individual cells directly from in situ samples have great potential for in-depth analysis of the structure and function of microbiomes.In this work,based on an artificial intel...Identification,sorting,and sequencing of individual cells directly from in situ samples have great potential for in-depth analysis of the structure and function of microbiomes.In this work,based on an artificial intelligence(AI)-assisted object detection model for cell phenotype screening and a cross-interface contact method for single-cell exporting,we developed an automatic and index-based system called EasySort AUTO,where individual microbial cells are sorted and then packaged in a microdroplet and automatically exported in a precisely indexed,“One-Cell-One-Tube”manner.The target cell is automatically identified based on an AI-assisted object detection model and then mobilized via an optical tweezer for sorting.Then,a crossinterface contact microfluidic printing method that we developed enables the automated transfer of cells from the chip to the tube,which leads to coupling with subsequent single-cell culture or sequencing.The efficiency of the system for single-cell printing is>93%.The throughput of the system for single-cell printing is~120 cells/h.Moreover,>80%of single cells of both yeast and Escherichia coli are culturable,suggesting the superior preservation of cell viability during sorting.Finally,AI-assisted object detection supports automated sorting of target cells with high accuracy from mixed yeast samples,which was validated by downstream single-cell proliferation assays.The automation,index maintenance,and vitality preservation of EasySort AUTO suggest its excellent application potential for single-cell sorting.展开更多
Kluyveromyces marxianus is a food-safe yeast with great potential for producing heterologous proteins.Improving the yield in K.marxianus remains a challenge and incorporating large-scale functional modules poses a tec...Kluyveromyces marxianus is a food-safe yeast with great potential for producing heterologous proteins.Improving the yield in K.marxianus remains a challenge and incorporating large-scale functional modules poses a technical obstacle in engineering.To address these issues,linear and circular yeast artificial chromosomes of K.marxianus(KmYACs)were constructed and loaded with disulfide bond formation modules from Pichia pastoris or K.marxianus.These modules contained up to seven genes with a maximum size of 15 kb.KmYACs carried telomeres either from K.marxianus or Tetrahymena.KmYACs were transferred successfully into K.marxianus and stably propagated without affecting the normal growth of the host,regardless of the type of telomeres and configurations of KmYACs.KmYACs increased the overall expression levels of disulfide bond formation genes and significantly enhanced the yield of various heterologous proteins.In high-density fermentation,the use of KmYACs resulted in a glucoamylase yield of 16.8 g/l,the highest reported level to date in K.marxianus.Transcriptomic and metabolomic analysis of cells containing KmYACs suggested increased flavin adenine dinucleotide biosynthesis,enhanced flux entering the tricarboxylic acid cycle,and a preferred demand for lysine and arginine as features of cells overexpressing heterologous proteins.Consistently,supplementing lysine or arginine further improved the yield.Therefore,KmYAC provides a powerful platform for manipulating large modules with enormous potential for industrial applications and fundamental research.Transferring the disulfide bond formation module via YACs proves to be an efficient strategy for improving the yield of heterologous proteins,and this strategy may be applied to optimize other microbial cell factories.展开更多
Antibiotic resistance in gram-negative pathogens has become one of the most serious global public health threats.The role of the N-acyl homoserine lactone(AHL)-mediated signaling pathway,which is widespread in gram-ne...Antibiotic resistance in gram-negative pathogens has become one of the most serious global public health threats.The role of the N-acyl homoserine lactone(AHL)-mediated signaling pathway,which is widespread in gram-negative bacteria,in the bacterial resistance process should be studied in depth.Here,we report a degrading enzyme of AHLs,MomL,that inhibits the antibiotic resistance of Pseudomonas aeruginosa through a novel mechanism.The MomL-mediated reactivation of kanamycin is highly associated with the relA-mediated starvation stringent response.The degradation of AHLs by MomL results in the inability of LasR to activate relA,which,in turn,stops the activation of downstream rpoS.Further results show that rpoS directly regulates the type VI secretion system H2-T6SS.Under MomL treatment,inactivated RpoS fails to regulate H2-T6SS;therefore,the expression of effector phospholipase A is reduced,and the adaptability of bacteria to antibiotics is weakened.MomL in combination with kanamycin is effective against a wide range of gram-negative pathogenic bacteria.Therefore,this study reports a MomL-antibiotic treatment strategy on antibiotic-resistant bacteria and reveals its mechanism of action.展开更多
Anaerobic microbial corrosion of iron-containing metals causes extensive economic damage.Some microbes are capable of direct metal-to-microbe electron transfer(electrobiocorrosion),but the prevalence of electrobiocorr...Anaerobic microbial corrosion of iron-containing metals causes extensive economic damage.Some microbes are capable of direct metal-to-microbe electron transfer(electrobiocorrosion),but the prevalence of electrobiocorrosion among diverse methanogens and acetogens is poorly understood because of a lack of tools for their genetic manipulation.Previous studies have suggested that respiration with 316L stainless steel as the electron donor is indicative of electrobiocorrosion,because,unlike pure Fe^(0),316L stainless steel does not abiotically generate H_(2) as an intermediary electron carrier.Here,we report that all of the methanogens(Methanosarcina vacuolata,Methanothrix soehngenii,and Methanobacterium strain IM1)and acetogens(Sporomusa ovata and Clostridium ljungdahli)evaluated respired with pure Fe^(0)as the electron donor,but only M.vacuolata,Mx.soehngeni,and S.ovata were capable of stainless steel electrobiocorrosion.The electrobiocorrosive methanogens re-quired acetate as an additional energy source in order to produce methane from stainless steel.Cocultures of S.ovata and Mx.soehngeni demonstrated how acetogens can provide acetate to methanogens during corrosion.Not only was Meth-anobacterium strain IM1 not capable of electrobiocorrosion,but it also did not accept electrons from Geobacter metal-lireducens,an effective electron-donating partner for direct interspecies electron transfer to all methanogens that can directly accept electrons from Fe^(0).The finding that M.vacuolata,Mx.soehngeni,and S.ovata are capable of electrobiocorrosion,despite a lack of the outer-surface c-type cytochromes previously found to be important in other electrobiocorrosive microbes,demonstrates that there are multiple microbial strategies for making electrical contact with Fe^(0).展开更多
Staphylococcus aureus is a common cause of diverse infections,ranging from superficial to invasive,affecting both humans and animals.The widespread use of antibiotics in clinical treatments has led to the emergence of...Staphylococcus aureus is a common cause of diverse infections,ranging from superficial to invasive,affecting both humans and animals.The widespread use of antibiotics in clinical treatments has led to the emergence of antibiotic-resistant strains and small colony variants.This surge presents a significant challenge in eliminating infections and undermines the efficacy of available treatments.The bacterial Save Our Souls(Sos)response,triggered by genotoxic stressors,encompasses host immune defenses and antibiotics,playing a crucial role in bacterial survival,invasiveness,virulence,and drug resistance.Accumulating evidence underscores the pivotal role of the Sos response system in the pathogenicity of S.aureus.Inhibiting this system offers a promising approach for effective bactericidal treatments and curbing the evolution of antimicrobial re-sistance.Here,we provide a comprehensive review of the activation,impact,and key proteins associated with the Sos response in S.aureus.Additionally,perspectives on therapeutic strategies targeting the Sos response for S.aureus,both individually and in combination with traditional antibiotics are proposed.展开更多
Impactstatement Earth's lower near space of 20-40 km above sea level with polyextreme conditions serves as a unique Mars analog for astrobiological research to investigate the limits of life on Earth and planetary...Impactstatement Earth's lower near space of 20-40 km above sea level with polyextreme conditions serves as a unique Mars analog for astrobiological research to investigate the limits of life on Earth and planetary protection considerations for Mars exploration.In this study,we exposed Mars-like desert regolith to near space at a float altitude of~35 km and isolated four bacterial strains after exposure.展开更多
Impact statement We have developed a manually curated online reference database,DANMEL(http://124.239.252.254/danmel/),that addresses the lack of accurate dissection and annotation of the genetic structures of mobile ...Impact statement We have developed a manually curated online reference database,DANMEL(http://124.239.252.254/danmel/),that addresses the lack of accurate dissection and annotation of the genetic structures of mobile genetic elements(MGEs)with genes for drug resistance.DANMEL contains accurately annotated and genetically dissected reference MGEs covering 5 categories and 135 subcategories/subfamilies of MGEs.Further,DANMEL provides a detailed guide on how to precisely annotate MGEs.DANMEL also provides SEARCH/BLAST functions to facilitate finding reference MGEs.Overall,DANMEL will aid researchers to conduct in-depth genetic analysis of sequenced bacterial MGEs with drug-resistance genes and further facilitate a better understanding of bacterial MGEs associated with drug resistance at a genomic level.展开更多
Pseudomonas aeruginosa is a ubiquitous and metabolically versatile microorganism naturally found in soil and water.It is also an opportunistic pathogen in plants,insects,animals,and humans.In response to increasing ce...Pseudomonas aeruginosa is a ubiquitous and metabolically versatile microorganism naturally found in soil and water.It is also an opportunistic pathogen in plants,insects,animals,and humans.In response to increasing cell density,P.aeruginosa uses two acylhomoserine lactone(AHL)quorum-sensing(QS)signals(i.e.,N-3-oxo-dodecanoyl homoserine lactone[3-oxo-C12-HSL]and Nbutanoyl-homoserine lactone[C4-HsL]),which regulate the expression of hundreds of genes.However,how the biosynthesis of these two QS signals is coordinated remains unknown.We studied the regulation of these two QS signals in the rhizosphere strain PA1201.PA1201 sequentially produced 3-oxo-C12-HSL and C4-HSL at the early and late growth stages,respectively.The highest 3-oxo-C12-HSL-dependent elastase activity was observed at the early stage,while the highest C4-HSL-dependent rhamnolipid production was observed at the late stage.The atypical regulator RsaL played a pivotal role in coordinating 3-oxo-C12-HSL and C4-HSL biosynthesis and QS-associated virulence.RsaL repressed las/transcription by binding the-10 and-35 boxes of the lasl promoter.In contrast,RsaL activated rhll transcription by binding the region encoding the 5'-untranslated region of the rhll mRNA.Further,RsaL repressed its own expression by binding a nucleotide motif located in the-35 box of the rsaL promoter.Thus,RsaL acts as a molecular switch that coordinates the sequential biosynthesis of AHL QS signals and differential virulence in PA1201.Finally,C4-HSL activation by RsaL was independent of the Las and Pseudomonas quinolone signal(PQS)QS signaling systems.Therefore,we propose a new model of the QS regulatory network in PA1201,in which RsaL represents a superior player acting at the top of the hierarchy.展开更多
文摘Fungi are an integral part of the earth's biosphere.They are broadly distributed in all continents and ecosystems and play a diversity of roles.Here,I review our current understanding of fungal threats to humans and describe the major factors that contribute to various threats.Among the 140,000 or so known species out of the estimated six million fungal species on Earth,about 10%directly or indirectly threaten human health and welfare.Major threats include mushroom poisoning,fungal allergies,infections of crop plants,food contamination by mycotoxins,and mycoses in humans.A growing number of factors have been identified to impact various fungal threats,including human demographics,crop distributions,anthropogenic activities,pathogen dispersals,global climate change,and/or the applications of antifungal drugs and agricultural fungicides.However,while models have been developed for analyzing various processes of individual threats and threat managements,current data are primarily descriptive and incomplete,and there are significant obstacles to integration of the diverse factors into accurate quantitative assessments of fungal threats.With increasing technological advances and concerted efforts to track the spatial and temporal data on climate and environmental variables;mycotoxins in the feed and food supply chains;fungal population dynamics in crop fields,human and animal populations,and the environment;human population demographics;and the prevalence and severities of fungal allergies and diseases,our ability to accurately assess fungal threats will improve.Such improvements should help us develop holistic strategies to manage fungal threats in the future.
基金supported by the National Key Research Program of China(grant no.2019YFE0191000)the 13th Five-year Informatization Plan of the Chinese Academy of Sciences(grant nos.XXH13506,XXH13505)the National Science Foundation for Young Scientists of China(grant no.31701157).
文摘Impact Statement We present a method of mapping data from publicly available genomics and publication resources to the Resource Description Framework(RDF)and implement a server to publish linked open data(LOD).As one of the largest and most comprehensive semantic databases about coronaviruses,the resulted gcCov database demonstrates the capability of using data in the LOD framework to promote correlations between genotypes and phenotypes.These correlations will be helpful for future research on fundamental viral mechanisms and drug and vaccine designs.
基金supported financially by the Natural Science Foundation of China(Grants 42276139,42230401,42141003,41921006,92051116,91951209)2030 Project,Shanghai Jiao Tong University(Grant WH510244001)the National Postdoctoral Program for Innovative Talents(Grant No.BX20190204).
文摘Lignin degradation is a major process in the global carbon cycle across both terrestrial and marine ecosystems.Bathyarchaeia,which are among the most abundant microorganisms in marine sediment,have been proposed to mediate anaerobic lignin degradation.However,the mechanism of bathyarchaeial lignin degradation remains unclear.Here,we report an enrichment culture of Bathy-archaeia,named Candidatus Baizosediminiarchaeum ligniniphilus DL1YTT001(Ca.B.ligniniphilus),from coastal sediments that can grow with lignin as the sole organic carbon source under mesophilic anoxic conditions.Ca.B.ligniniphilus possesses and highly expresses novel methyltransferase 1(MT1,mtgB)for transferring methoxyl groups from lignin monomers to cob(I)alamin.MtgBs have no homology with known microbial methyltransferases and are present only in bathyarchaeial lineages.Heterologous expression of the mtgB gene confirmed O-demethylation activity.The mtgB genes were identified in metagenomic data sets from a wide range of coastal sediments,and they were highly expressed in coastal sediments from the East China Sea.These findings suggest that Bathyarchaeia,capable of O-demethylation via their novel and specific methyltransferases,are ubiquitous in coastal sediments.
基金financially supported by the National Natural Science Foundation of China(Nos.82170342,T2288101,82303578,and 82372626)the Fundamental Research Project for Shanghai Municipal Health Commission(20214Y0328 and 23YF1438700)the Fundamental Research Funds for Minhang Hospital(No.2023MHBJ01).
文摘Atherosclerosis is a chronic inflammatory metabolic disease with a complex pathogenesis.However,the exact details of its pathogenesis are still unclear,which limits effective clinical treatment of atherosclerosis.Recently,multiple studies have demonstrated that the gut microbiota plays a pivotal role in the onset and progression of atherosclerosis.This review discusses possible treatments for atherosclerosis using the gut microbiome as an intervention target and summarizes the role of the gut microbiome and its metabolites in the development of atherosclerosis.New strategies for the treatment of atherosclerosis are needed.This review provides clues for further research on the mechanisms of the relationship between the gut microbiota and atherosclerosis.
基金We are grateful to the National Natural Science Foundation of China(Grants 22122702,21735004,and 21775128)Innovative research team of high‐level local universities in Shanghai(SHSMU‐ZLCX20212601).
文摘Despite the fast progress in our understanding of the complex functions of gut microbiota,it is still challenging to directly investigate the in vivo microbial activities and processes on an individual cell basis.To gain knowledge of the indigenous growth/division patterns of the diverse mouse gut bacteria with a relatively high throughput,here,we propose an integrative strategy,which combines the use of fluorescent probe labeling,confocal imaging with single‐cell sorting,and sequencing.Mouse gut bacteria sequentially labeled by two fluorescent D‐amino acid probes in vivo were first imaged by confocal microscopy to visualize their growth patterns,which can be unveiled by the distribution of the two fluorescence signals on each bacterium.Bacterial cells of interest on the imaging slide were then sorted using a laser ejection equipment,and the collected cells were then sequenced individually to identify their taxa.Our strategy allows integrated acquirement of the growth pattern knowledge of a variety of gut bacteria and their genomic information on a single‐cell basis,which should also have great potential in studying many other complex bacterial systems.
基金funded by the National Natural Science Foundation of China(32371687).
文摘Impact statement.Evolutionary training of phages can help to counter bacterial resistance evolution.Here,we address whether metapopulation processes can enhance the evolution of phage infectivity.Our experiment with a model bacterium-phage system supported a prediction of long-term fluctuating selection dynamics.Specifically,metapopulations of several small habitats showed greater total infectivity ranges by supporting more diverse phages,compared with single large populations.
基金This study was supported by the National Natural Science Foundation of China(NSFC)grant 82172288.
文摘The human gut is home to nearly 100 trillion microbes1,which constitute the human gut microecological system.The microbiota–gut–brain(MGB)axis is a two‐way communication pathway between gut microbiota and the brain through the immune system,metabolism,and the enteric nervous system.An increasing amount of clinical evidence indicates that abnormal MBG axis communication caused by intestinal ecosystem imbalance can affect the development of many neurological diseases,such as Parkinson's disease,Alzheimer's disease,and autism spectrum disorder(ASD)2.
基金supported by the National Natural Science Foundation of China(92251301[A.L.],22008252[B.W.],and 91851211[L.S.])the National Key Research and Development Program of China(2019YFC1805900[A.L.],2018YFA0901303[L.S.],and 2022YFA0912800[B.W.]).
文摘Photosynthesis has been the cornerstone of solar energy conversion on Earth for billions of years,crucial for sustaining the biosphere and maintaining the carbon and water cycles.However,with the rise of industrial civilization,natural photosynthesis alone has become insufficient to meet growing energy and product demands1,leading to extensive fossil fuel use,environmental pollution,and energy crises.In response,scientists have sought to enhance natural photosynthesis through genetic engineering and synthetic biology2,or to develop alternative solar conversion methods using advanced materials science3.
基金funded by grants from the National Key Research and Development Plan of China(2021YFC2300200,2020YFC1200100,and 2018YFA0507202)the National Natural Science Foundation of China(31825001,81730063,32188101,82102389,and 81961160737)+5 种基金the Tsinghua University Spring Breeze Fund(2020Z99CFG017)the Shenzhen Science and Technology Project(JSGG20191129144225464)the Shenzhen San‐Ming Project for Prevention and Research on Vector‐borne Diseases(SZSM201611064)the Young Elite Scientists Sponsorship Program(2021QNRC001)the Yunnan Cheng Gong Expert Work‐Station(202005AF150034)We acknowledge the provincial innovation team for the prevention and control of highly pathogenic pathogens,Institute of Medical Biology,Chinese Academy of Medical Science(202105AE160020).
文摘As the largest organ of the body,the skin acts as a barrier to prevent diseases and harbors a variety of beneficial bacteria.Furthermore,the skin bacterial microbiota plays a vital role in health and disease.Disruption of the barrier or an imbalance between symbionts and pathogens can lead to skin disorders or even systemic diseases.In this review,we first provide an overview of research on skin bacterial microbiota and human health,including the composition of skin bacteria in a healthy state,as well as skin bacterial microbiota educating the immune system and preventing the invasion of pathogens.We then discuss the diseases that result from skin microbial dysbiosis,including atopic dermatitis,common acne,chronic wounds,psoriasis,viral transmission,cutaneous lupus,cutaneous lymphoma,and hidradenitis suppurativa.Finally,we highlight the progress that utilizes skin microorganisms for disease therapeutics,such as bacteriotherapy and skin microbiome transplantation.A deeper knowledge of the interaction between human health and disease and the homeostasis of the skin bacterial microbiota will lead to new insights and strategies for exploiting skin bacteria as a novel therapeutic target.
文摘Marine microbiomes are integral to the functioning of a healthy ocean and have the potential to be key contributors toward an all-Atlantic sustainable blue bioeconomy(Figure 1).New compounds may be developed based on these microbiomes.The Atlantic Ocean is a biodiversity hotspot.The All-Atlantic Ocean Research and Innovation Alliance(AAORIA)Declaration,signed in 2022 in Washington,DC,is a promising mechanism to move forward marine microbiome science,technology,and innovation.
基金supported by the National Key R&D Program of China(2022YFD1300404)the National Natural Science Foundation of China(31930106 and U22A20514)+1 种基金the 2115 Talent Development Program of China Agricultural University(1041-00109019)the Pinduoduo-China Agricultural University Research Fund(PC2023A01001).
文摘Broad-spectrum antibacterial drugs often lack specificity,leading to indiscriminate bactericidal activity,which can disrupt the normal microbial balance of the host flora and cause unnecessary cytotoxicity during systemic administration.In this study,we constructed a specifically targeted antimicrobial peptide against Staphylococcus aureus by introducing a phage-displayed peptide onto a broad-spectrum antimicrobial peptide and explored its structure–function relationship through one-factor modification.SFK2 obtained by screening based on the selectivity index and the targeting index showed specific killing ability against S.aureus.Moreover,SFK2 showed excellent biocompatibility in mice and piglet,and demonstrated significant therapeutic efficacy against S.aureus infection.In conclusion,our screening of phage-derived heptapeptides effectively enhances the specific bactericidal ability of the antimicrobial peptides against S.aureus,providing a theoretical basis for developing targeted antimicrobial peptides.
基金supported by the grants from the National Key Research and Development Program of China(No.2020YFA0907300)the National Natural Science Foundation of China(Nos.U2006219 and 52301080).
文摘Sulfate-reducing microorganisms extensively contribute to the corrosion of ferrous metal infrastructure.There is substantial debate over their corrosion mechanisms.We investigated Fe^(0) corrosion with Desulfovibrio vulgaris,the sulfate reducer most often employed in corrosion studies.Cultures were grown with both lactate and Fe^(0) as potential electron donors to replicate the common environmental condition in which organic substrates help fuel the growth of corrosive microbes.Fe^(0) was corroded in cultures of a D.vulgaris hydrogenase-deficient mutant with the 1:1 correspondence between Fe^(0) loss and H_(2) accumulation expected for Fe^(0) oxidation coupled to H+reduction to H_(2).This result and the extent of sulfate reduction indicated that D.vulgaris was not capable of direct Fe^(0)-to-microbe electron transfer even though it was provided with a supplementary energy source in the presence of abundant ferrous sulfide.Corrosion in the hydrogenase-deficient mutant cultures was greater than in sterile controls,demonstrating that H_(2) removal was not necessary for the enhanced corrosion observed in the presence of microbes.The parental H_(2)-consuming strain corroded more Fe^(0) than the mutant strain,which could be attributed to H_(2) oxidation coupled to sulfate reduction,producing sulfide that further stimulated Fe^(0) oxidation.The results suggest that H_(2) consumption is not necessary for microbially enhanced corrosion,but H_(2) oxidation can indirectly promote corrosion by increasing sulfide generation from sulfate reduction.The finding that D.vulgaris was incapable of direct electron uptake from Fe^(0) reaffirms that direct metal-to-microbe electron transfer has yet to be rigorously described in sulfate-reducing microbes.
基金the National Key R&D Program of China(Grant No.2021YFC2101100).
文摘Identification,sorting,and sequencing of individual cells directly from in situ samples have great potential for in-depth analysis of the structure and function of microbiomes.In this work,based on an artificial intelligence(AI)-assisted object detection model for cell phenotype screening and a cross-interface contact method for single-cell exporting,we developed an automatic and index-based system called EasySort AUTO,where individual microbial cells are sorted and then packaged in a microdroplet and automatically exported in a precisely indexed,“One-Cell-One-Tube”manner.The target cell is automatically identified based on an AI-assisted object detection model and then mobilized via an optical tweezer for sorting.Then,a crossinterface contact microfluidic printing method that we developed enables the automated transfer of cells from the chip to the tube,which leads to coupling with subsequent single-cell culture or sequencing.The efficiency of the system for single-cell printing is>93%.The throughput of the system for single-cell printing is~120 cells/h.Moreover,>80%of single cells of both yeast and Escherichia coli are culturable,suggesting the superior preservation of cell viability during sorting.Finally,AI-assisted object detection supports automated sorting of target cells with high accuracy from mixed yeast samples,which was validated by downstream single-cell proliferation assays.The automation,index maintenance,and vitality preservation of EasySort AUTO suggest its excellent application potential for single-cell sorting.
基金supported by the National Key Research and Development Program of China(Nos.2021YFA0910601 and 2021YFC2100203)Shanghai Municipal Education Commission(2021-03-52)Science and Technology Research Program of Shanghai(19DZ2282100).
文摘Kluyveromyces marxianus is a food-safe yeast with great potential for producing heterologous proteins.Improving the yield in K.marxianus remains a challenge and incorporating large-scale functional modules poses a technical obstacle in engineering.To address these issues,linear and circular yeast artificial chromosomes of K.marxianus(KmYACs)were constructed and loaded with disulfide bond formation modules from Pichia pastoris or K.marxianus.These modules contained up to seven genes with a maximum size of 15 kb.KmYACs carried telomeres either from K.marxianus or Tetrahymena.KmYACs were transferred successfully into K.marxianus and stably propagated without affecting the normal growth of the host,regardless of the type of telomeres and configurations of KmYACs.KmYACs increased the overall expression levels of disulfide bond formation genes and significantly enhanced the yield of various heterologous proteins.In high-density fermentation,the use of KmYACs resulted in a glucoamylase yield of 16.8 g/l,the highest reported level to date in K.marxianus.Transcriptomic and metabolomic analysis of cells containing KmYACs suggested increased flavin adenine dinucleotide biosynthesis,enhanced flux entering the tricarboxylic acid cycle,and a preferred demand for lysine and arginine as features of cells overexpressing heterologous proteins.Consistently,supplementing lysine or arginine further improved the yield.Therefore,KmYAC provides a powerful platform for manipulating large modules with enormous potential for industrial applications and fundamental research.Transferring the disulfide bond formation module via YACs proves to be an efficient strategy for improving the yield of heterologous proteins,and this strategy may be applied to optimize other microbial cell factories.
基金the National Natural Science Foundation of China(Nos.42176108 and 31870023)the Young Taishan Scholars Program of Shandong Province(No.tsqn202103029)+2 种基金the Marine S&T Fund of Shandong Province for Pilot National Laboratory for Marine Science and Technology(Qingdao)(No.2018SDKJ0406-4)the Fundamental Research Funds for the Central Universities(No.201941009)the open research funds of the State Key Laboratory of Ophthalmology(No.303060202400368).
文摘Antibiotic resistance in gram-negative pathogens has become one of the most serious global public health threats.The role of the N-acyl homoserine lactone(AHL)-mediated signaling pathway,which is widespread in gram-negative bacteria,in the bacterial resistance process should be studied in depth.Here,we report a degrading enzyme of AHLs,MomL,that inhibits the antibiotic resistance of Pseudomonas aeruginosa through a novel mechanism.The MomL-mediated reactivation of kanamycin is highly associated with the relA-mediated starvation stringent response.The degradation of AHLs by MomL results in the inability of LasR to activate relA,which,in turn,stops the activation of downstream rpoS.Further results show that rpoS directly regulates the type VI secretion system H2-T6SS.Under MomL treatment,inactivated RpoS fails to regulate H2-T6SS;therefore,the expression of effector phospholipase A is reduced,and the adaptability of bacteria to antibiotics is weakened.MomL in combination with kanamycin is effective against a wide range of gram-negative pathogenic bacteria.Therefore,this study reports a MomL-antibiotic treatment strategy on antibiotic-resistant bacteria and reveals its mechanism of action.
文摘Anaerobic microbial corrosion of iron-containing metals causes extensive economic damage.Some microbes are capable of direct metal-to-microbe electron transfer(electrobiocorrosion),but the prevalence of electrobiocorrosion among diverse methanogens and acetogens is poorly understood because of a lack of tools for their genetic manipulation.Previous studies have suggested that respiration with 316L stainless steel as the electron donor is indicative of electrobiocorrosion,because,unlike pure Fe^(0),316L stainless steel does not abiotically generate H_(2) as an intermediary electron carrier.Here,we report that all of the methanogens(Methanosarcina vacuolata,Methanothrix soehngenii,and Methanobacterium strain IM1)and acetogens(Sporomusa ovata and Clostridium ljungdahli)evaluated respired with pure Fe^(0)as the electron donor,but only M.vacuolata,Mx.soehngeni,and S.ovata were capable of stainless steel electrobiocorrosion.The electrobiocorrosive methanogens re-quired acetate as an additional energy source in order to produce methane from stainless steel.Cocultures of S.ovata and Mx.soehngeni demonstrated how acetogens can provide acetate to methanogens during corrosion.Not only was Meth-anobacterium strain IM1 not capable of electrobiocorrosion,but it also did not accept electrons from Geobacter metal-lireducens,an effective electron-donating partner for direct interspecies electron transfer to all methanogens that can directly accept electrons from Fe^(0).The finding that M.vacuolata,Mx.soehngeni,and S.ovata are capable of electrobiocorrosion,despite a lack of the outer-surface c-type cytochromes previously found to be important in other electrobiocorrosive microbes,demonstrates that there are multiple microbial strategies for making electrical contact with Fe^(0).
基金This work was supported by the National Natural Science Foundation of China(32270043 and 32100017)the Natural Science Foundation of Zhejiang Province(LQ22C050002)+2 种基金the State Key Laboratory Foundation for Diagnosis and Treatment of Infectious Diseases to KC(zz202309)the Hangzhou Youth Innovation Team Project(TD2023020)the Scientific Research Foundation for Scholars of HZNU(4125C50221204040).
文摘Staphylococcus aureus is a common cause of diverse infections,ranging from superficial to invasive,affecting both humans and animals.The widespread use of antibiotics in clinical treatments has led to the emergence of antibiotic-resistant strains and small colony variants.This surge presents a significant challenge in eliminating infections and undermines the efficacy of available treatments.The bacterial Save Our Souls(Sos)response,triggered by genotoxic stressors,encompasses host immune defenses and antibiotics,playing a crucial role in bacterial survival,invasiveness,virulence,and drug resistance.Accumulating evidence underscores the pivotal role of the Sos response system in the pathogenicity of S.aureus.Inhibiting this system offers a promising approach for effective bactericidal treatments and curbing the evolution of antimicrobial re-sistance.Here,we provide a comprehensive review of the activation,impact,and key proteins associated with the Sos response in S.aureus.Additionally,perspectives on therapeutic strategies targeting the Sos response for S.aureus,both individually and in combination with traditional antibiotics are proposed.
基金This study was supported by the National Natural Science Foundation of China(NSFC)grant T2225011the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA17010501).
文摘Impactstatement Earth's lower near space of 20-40 km above sea level with polyextreme conditions serves as a unique Mars analog for astrobiological research to investigate the limits of life on Earth and planetary protection considerations for Mars exploration.In this study,we exposed Mars-like desert regolith to near space at a float altitude of~35 km and isolated four bacterial strains after exposure.
文摘Impact statement We have developed a manually curated online reference database,DANMEL(http://124.239.252.254/danmel/),that addresses the lack of accurate dissection and annotation of the genetic structures of mobile genetic elements(MGEs)with genes for drug resistance.DANMEL contains accurately annotated and genetically dissected reference MGEs covering 5 categories and 135 subcategories/subfamilies of MGEs.Further,DANMEL provides a detailed guide on how to precisely annotate MGEs.DANMEL also provides SEARCH/BLAST functions to facilitate finding reference MGEs.Overall,DANMEL will aid researchers to conduct in-depth genetic analysis of sequenced bacterial MGEs with drug-resistance genes and further facilitate a better understanding of bacterial MGEs associated with drug resistance at a genomic level.
基金financially supported by grants from the National Key R&D Program of China(2018YFA0901900 to H.Y.W.)the National Natural Science Foundation of China(No.31972231 to H.Y.W)。
文摘Pseudomonas aeruginosa is a ubiquitous and metabolically versatile microorganism naturally found in soil and water.It is also an opportunistic pathogen in plants,insects,animals,and humans.In response to increasing cell density,P.aeruginosa uses two acylhomoserine lactone(AHL)quorum-sensing(QS)signals(i.e.,N-3-oxo-dodecanoyl homoserine lactone[3-oxo-C12-HSL]and Nbutanoyl-homoserine lactone[C4-HsL]),which regulate the expression of hundreds of genes.However,how the biosynthesis of these two QS signals is coordinated remains unknown.We studied the regulation of these two QS signals in the rhizosphere strain PA1201.PA1201 sequentially produced 3-oxo-C12-HSL and C4-HSL at the early and late growth stages,respectively.The highest 3-oxo-C12-HSL-dependent elastase activity was observed at the early stage,while the highest C4-HSL-dependent rhamnolipid production was observed at the late stage.The atypical regulator RsaL played a pivotal role in coordinating 3-oxo-C12-HSL and C4-HSL biosynthesis and QS-associated virulence.RsaL repressed las/transcription by binding the-10 and-35 boxes of the lasl promoter.In contrast,RsaL activated rhll transcription by binding the region encoding the 5'-untranslated region of the rhll mRNA.Further,RsaL repressed its own expression by binding a nucleotide motif located in the-35 box of the rsaL promoter.Thus,RsaL acts as a molecular switch that coordinates the sequential biosynthesis of AHL QS signals and differential virulence in PA1201.Finally,C4-HSL activation by RsaL was independent of the Las and Pseudomonas quinolone signal(PQS)QS signaling systems.Therefore,we propose a new model of the QS regulatory network in PA1201,in which RsaL represents a superior player acting at the top of the hierarchy.
