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
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
Salmonella and their biofilm formation are the primary bacterial causes of foodborne outbreaks and crosscontamination. The objective of the study was to investigate the potential of Salmonella phages as an alternative...Salmonella and their biofilm formation are the primary bacterial causes of foodborne outbreaks and crosscontamination. The objective of the study was to investigate the potential of Salmonella phages as an alternative technology for biofilm removal. In this work, 21 Salmonella phages were isolated from a chicken farm and slaughter plant and the phage(CW1)with the broadest spectrum was characterized. Complete genome sequence analysis revealed that the genomes of phage CW1 is composed of 41 763 bp with 58 open reading frames(ORFs)and a holin-endolysin system and it does not encode any virulence or lysogeny. A phage cocktail consisted of CW1(with the broadest spectrum of 70.49%)and CW11, M4 and M10(with a high lytic activity of more than 67.11%)was established. Treatment with the cocktail reduced the cells in the developing biofilm and mature biofilm by 0.79 lg(CFU/cm~2)and 0.4 lg(CFU/cm~2), respectively. More dead cells and scattered extracellular polymeric substances(EPS)were observed by confocal laser scanning microscopy and scanning electron microscopy. Raman analysis found that carbohydrates and proteins were the identification receptors for scattered EPS. This finding suggests that this phage cockta il has potential applications for the sterilization of Salmonella biofilm during meat processing.展开更多
African swine fever virus(ASFV)is a lethal pathogen that causes severe threats to the global swine industry and it has already had catastrophic socio-economic effects.To date,no licensed prophylactic vaccine exists.Li...African swine fever virus(ASFV)is a lethal pathogen that causes severe threats to the global swine industry and it has already had catastrophic socio-economic effects.To date,no licensed prophylactic vaccine exists.Limited knowledge exists about the major immunogens of ASFV and the epitope mapping of the key antigens.As such,there is a considerable requirement to understand the functional monoclonal antibodies(mAbs)and the epitope mapping may be of utmost importance in our understanding of immune responses and designing improved vaccines,therapeutics,and diagnostics.In this study,we generated an ASFV antibody phage-display library from ASFV convalescent swine PBMCs,further screened a specific ASFV major capsid protein(p72)single-chain antibody and fused with an IgG Fc fragment(scFv-83-Fc),which is a specific recognition antibody against ASFV Pig/HLJ/2018 strain.Using the scFv-83-Fc mAb,we selected a conserved epitope peptide(221MTGYKH226)of p72 retrieved from a phage-displayed random peptide library.Moreover,flow cytometry and cell uptake experiments demonstrated that the epitope peptide can significantly promote BMDCs maturation in vitro and could be effectively uptaken by DCs,which indicated its potential application in vaccine and diagnostic reagent development.Overall,this study provided a valuable platform for identifying targets for ASFV vaccine development,as well as to facilitate the optimization design of subunit vaccine and diagnostic reagents.展开更多
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.
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.
基金funded by grants from the National Natural Science Foundation of China (31872911)the National Key Research Program of China (2018YFC1603800)。
文摘Salmonella and their biofilm formation are the primary bacterial causes of foodborne outbreaks and crosscontamination. The objective of the study was to investigate the potential of Salmonella phages as an alternative technology for biofilm removal. In this work, 21 Salmonella phages were isolated from a chicken farm and slaughter plant and the phage(CW1)with the broadest spectrum was characterized. Complete genome sequence analysis revealed that the genomes of phage CW1 is composed of 41 763 bp with 58 open reading frames(ORFs)and a holin-endolysin system and it does not encode any virulence or lysogeny. A phage cocktail consisted of CW1(with the broadest spectrum of 70.49%)and CW11, M4 and M10(with a high lytic activity of more than 67.11%)was established. Treatment with the cocktail reduced the cells in the developing biofilm and mature biofilm by 0.79 lg(CFU/cm~2)and 0.4 lg(CFU/cm~2), respectively. More dead cells and scattered extracellular polymeric substances(EPS)were observed by confocal laser scanning microscopy and scanning electron microscopy. Raman analysis found that carbohydrates and proteins were the identification receptors for scattered EPS. This finding suggests that this phage cockta il has potential applications for the sterilization of Salmonella biofilm during meat processing.
基金supported by the National Natural Science Foundation of China(31941001 and 32002292)the Major Science and Technology Project of Henan Province,China(221100110600)the Natural Science Foundation of Henan Province(202300410199).
文摘African swine fever virus(ASFV)is a lethal pathogen that causes severe threats to the global swine industry and it has already had catastrophic socio-economic effects.To date,no licensed prophylactic vaccine exists.Limited knowledge exists about the major immunogens of ASFV and the epitope mapping of the key antigens.As such,there is a considerable requirement to understand the functional monoclonal antibodies(mAbs)and the epitope mapping may be of utmost importance in our understanding of immune responses and designing improved vaccines,therapeutics,and diagnostics.In this study,we generated an ASFV antibody phage-display library from ASFV convalescent swine PBMCs,further screened a specific ASFV major capsid protein(p72)single-chain antibody and fused with an IgG Fc fragment(scFv-83-Fc),which is a specific recognition antibody against ASFV Pig/HLJ/2018 strain.Using the scFv-83-Fc mAb,we selected a conserved epitope peptide(221MTGYKH226)of p72 retrieved from a phage-displayed random peptide library.Moreover,flow cytometry and cell uptake experiments demonstrated that the epitope peptide can significantly promote BMDCs maturation in vitro and could be effectively uptaken by DCs,which indicated its potential application in vaccine and diagnostic reagent development.Overall,this study provided a valuable platform for identifying targets for ASFV vaccine development,as well as to facilitate the optimization design of subunit vaccine and diagnostic reagents.
