Background Over the past few decades,antimicrobial resistance(AMR)has emerged as a global health challenge in human and veterinary medicine.Research on AMR genes in captive wild animals has increased.However,the prese...Background Over the past few decades,antimicrobial resistance(AMR)has emerged as a global health challenge in human and veterinary medicine.Research on AMR genes in captive wild animals has increased.However,the presence and molecular characteristics of tet(X)-carrying bacteria in these animals remain unknown.Methods Eighty-four samples were collected from captive wild animals.tet(X)variants were detected using polymerase chain reaction and the isolates were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.All isolated strains were subjected to antimicrobial susceptibility testing and whole-genome sequencing.The virulence of an Escherichia coli strain carrying enterotoxin genes was assessed using a Galleria mellonella larval model.Results We isolated two tet(X4)-positive E.coli strains and one tet(X4)-positive Raoultella ornithinolytica strain.Antimicrobial susceptibility tests revealed that all three tet(X4)-carrying bacteria were sensitive to the 13 tested antimicrobial agents,but exhibited resistance to tigecycline.Notably,one tet(X4)-carrying E.coli strain producing an enterotoxin had a toxic effect on G.mellonella larvae.Whole-genome sequencing analysis showed that the two tet(X4)-carrying E.coli strains had more than 95%similarity to tet(X4)-containing E.coli strains isolated from pigs and humans in China.Conclusion The genetic environment of tet(X4)closely resembled that of the plasmid described in previous studies.Our study identified tet(X4)-positive strains in wildlife and provided valuable epidemiological data for monitoring drug resistance.The identification of enterotoxin-producing E.coli strains also highlights the potential risks posed by virulence genes.展开更多
The rapid spread of mobile tigecycline resistance presents a significant public health threat,particularly with the increasing prevalence of tet(X4)-positive Enterobacterales across various species.This study aimed to...The rapid spread of mobile tigecycline resistance presents a significant public health threat,particularly with the increasing prevalence of tet(X4)-positive Enterobacterales across various species.This study aimed to inves-tigate the epidemic features and transmission dynamics of tet(X4)-positive Klebsiella pneumoniae(K.pneumo-niae)through the analysis of 206 raw meats,including pork(n=182),beef(n=16),duck(n=5),and chicken(n=3).These samples were collected from schools,markets,and restaurants in Chengdu City,China.A total of 25 isolates were obtained from 13 administrative regions.All isolates exhibited resistance to tetracycline,tigecycline,ampicillin,chloramphenicol,and florfenicol.Over half of the isolates also demon-strated resistance to streptomycin(80%),sulfamethoxazole/trimethoprim(72%),ciprofloxacin(64%),and ampicillin/sulbactam(56%).Among these strains,14 distinct sequence types(STs)were identified,revealing evidence of inter-regional clonal spread,notably among 9 K.pneumoniae ST3393.Phylogenetic analysis revealed the presence of two K.pneumoniae ST5 closely resembling hypervirulent K.pneumoniae from Jiangsu.Importantly,12 isolates were capable of transferring tigecycline resistance to Escherichia coli J53.Further plasmid analysis showed that the tet(X4)-harboring plasmids in K.pneumoniae could be classified into four types,primarily belonging to the IncFIA(HI1)/HI1A/HI1B hybrid plasmid(n=16)and IncFII plasmid(n=7),which significantly contributed to the cross-species dissemination of tet(X4).In summary,this study highlights the prevalence of MDR tet(X4)-positive K.pneumoniae in Chengdu,driven predominantly by clonal expansion and plasmid-mediated horizontal gene transfer.These findings emphasize the importance of contin-uous surveillance of tet(X4)-positive K.pneumoniae in raw meat and the implementation of effective measures to control their spread.展开更多
He and his colleagues[1]reported identification of the mobile resistance genes tet(X3)and tet(X4)on conjugative plasmids in Enterobacteriaceae and Acinetobacter isolated in China recently published in Nature Microbiol...He and his colleagues[1]reported identification of the mobile resistance genes tet(X3)and tet(X4)on conjugative plasmids in Enterobacteriaceae and Acinetobacter isolated in China recently published in Nature Microbiology.They noted that both tet(X3)and tet(X4)can confer resistance to tigecycline and the newly FDA-approved eravacycline and omadacyclin,which are last-resort antibiotics used to treat multi-drug-resistant(MDR)bacterial infections.Our previous report[2]revealed that live poultry market(LPM)is a huge antibiotic resistance gene(ARG)reservoir,including the mobile colistin resistance(mcr)genes,mcr-1,mcr-3,mcr-4 and mcr-5.Large-scale metagenomic data screening showed that tigecycline resistance gene tet(X3)was widespread in poultry faecal samples collected from China LPMs,whereas it has not been detected in human(n=2019)gut microbiomes[3],which suggested that tet(X3)is previously confined to animal guts or animal-derived bacteria.展开更多
The emergence and spread of plasmid-mediated tigecycline resistance genes have attracted extensive attention worldwide.We investigated the distribution of mobile tigecycline resistance genes in Salmonella genomes gene...The emergence and spread of plasmid-mediated tigecycline resistance genes have attracted extensive attention worldwide.We investigated the distribution of mobile tigecycline resistance genes in Salmonella genomes generated by both our laboratory and public bacterial genomes downloaded from the NCBI GenBank.The tet(X4)-positive strains were subjected to susceptibility testing and conjugation assays.The genetic features of the tet(X4)-bearing plasmid sequence were analyzed.Here,we report the identification of the plasmid-mediated tigecycline resistance gene tet(X4)in a conjugative plasmid of the Salmonella enterica serovar Llandoff strain SH16G3606,isolated from a man in China in 2016,the first reported serovar Llandoff in China as a novel sequence type ST8300.The tet(X4)-mediated resistance phenotype was successfully transferred from the Salmonella Llandoff strain into Escherichia coli J53,resulting in a 32-fold increase in the minimal inhibitory concentration of tigecycline.The tet(X4)gene was located between two copies of ISCR2 in the plasmid pSal21GXH-tetX4.To our knowledge,this is the first report of the plasmid-mediated tigecycline resistance gene tet(X4)in a Salmonella Llandoff strain isolated from a human stool sample in China.In addition,our findings demonstrated that a total of 171 isolates are carrying tet(X)-like genes distributed in 21 countries or areas across 6 continents,posing a serious threat to humans and public health.Overall,our timely discovery of the recent emergence of the tet(X4)gene in Salmonella isolates and other Enterobacteriaceae bacteria species supports the need for rapid surveillance to prevent the tet(X)-like gene from spreading.展开更多
The emergence of mobile Tigecycline-resistant tet(X3)and tet(X4)is believed to be a global threat to public health.Here,we investigated the prevalence of tet(X3)and tet(X4)in our metagenomic data of migratory birds.Wh...The emergence of mobile Tigecycline-resistant tet(X3)and tet(X4)is believed to be a global threat to public health.Here,we investigated the prevalence of tet(X3)and tet(X4)in our metagenomic data of migratory birds.While tet(X4)was not identified in our samples,tet(X3)was found in two gut microbiomes of bird fecal samples,with 100%amino acid identity of sites 150–387.These results suggest that tet(X3)has been spreading into the environment for a long period of time and that there is an urgent need to control its further transmission.展开更多
上调基因4(up-regulated gene-4,URG4)是受乙肝病毒X蛋白(hepatitis B virus X protein,HBx)激活的下游基因之一,最初在转染HBx的HepG2细胞中被克隆,因其上调细胞增殖效应而得名。研究发现,URG4在HBx转染后的HepG2细胞中表达明显增加,...上调基因4(up-regulated gene-4,URG4)是受乙肝病毒X蛋白(hepatitis B virus X protein,HBx)激活的下游基因之一,最初在转染HBx的HepG2细胞中被克隆,因其上调细胞增殖效应而得名。研究发现,URG4在HBx转染后的HepG2细胞中表达明显增加,同时细胞生长加速,存活率提高,表明URG4与乙肝病毒相关的肝细胞癌发生可能相关。近年来,人们发现URG4不仅在肝癌细胞中高表达,还与胃癌、骨肉瘤、非小细胞肺癌、神经母细胞瘤等多种癌症相关。本文结合近年来对URG4的研究成果,包括URG4基因及其蛋白质的结构与功能,URG4在癌症发生发展中的作用,以及在癌症早期诊断和预后中的意义进行综述,可望为后续深入地开展URG4与癌症的研究提供参考。展开更多
基金supported by the National Key Research and Development Program of China[grant number:2022YFD1800403]National Natural Science Foundation of China[grant number:82072341].
文摘Background Over the past few decades,antimicrobial resistance(AMR)has emerged as a global health challenge in human and veterinary medicine.Research on AMR genes in captive wild animals has increased.However,the presence and molecular characteristics of tet(X)-carrying bacteria in these animals remain unknown.Methods Eighty-four samples were collected from captive wild animals.tet(X)variants were detected using polymerase chain reaction and the isolates were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.All isolated strains were subjected to antimicrobial susceptibility testing and whole-genome sequencing.The virulence of an Escherichia coli strain carrying enterotoxin genes was assessed using a Galleria mellonella larval model.Results We isolated two tet(X4)-positive E.coli strains and one tet(X4)-positive Raoultella ornithinolytica strain.Antimicrobial susceptibility tests revealed that all three tet(X4)-carrying bacteria were sensitive to the 13 tested antimicrobial agents,but exhibited resistance to tigecycline.Notably,one tet(X4)-carrying E.coli strain producing an enterotoxin had a toxic effect on G.mellonella larvae.Whole-genome sequencing analysis showed that the two tet(X4)-carrying E.coli strains had more than 95%similarity to tet(X4)-containing E.coli strains isolated from pigs and humans in China.Conclusion The genetic environment of tet(X4)closely resembled that of the plasmid described in previous studies.Our study identified tet(X4)-positive strains in wildlife and provided valuable epidemiological data for monitoring drug resistance.The identification of enterotoxin-producing E.coli strains also highlights the potential risks posed by virulence genes.
基金supported by the National Key Research and Development Program of China(No.2022YFD1800400)National Natural Science Foundation of China(No.81991531)+1 种基金Natural Science Foundation of Shandong Province(No.ZR2020MC188)The sequence data of 25 K.pneumoniae isolates have been submitted to NCBI under BioProject accession number PRJNA1011004.
文摘The rapid spread of mobile tigecycline resistance presents a significant public health threat,particularly with the increasing prevalence of tet(X4)-positive Enterobacterales across various species.This study aimed to inves-tigate the epidemic features and transmission dynamics of tet(X4)-positive Klebsiella pneumoniae(K.pneumo-niae)through the analysis of 206 raw meats,including pork(n=182),beef(n=16),duck(n=5),and chicken(n=3).These samples were collected from schools,markets,and restaurants in Chengdu City,China.A total of 25 isolates were obtained from 13 administrative regions.All isolates exhibited resistance to tetracycline,tigecycline,ampicillin,chloramphenicol,and florfenicol.Over half of the isolates also demon-strated resistance to streptomycin(80%),sulfamethoxazole/trimethoprim(72%),ciprofloxacin(64%),and ampicillin/sulbactam(56%).Among these strains,14 distinct sequence types(STs)were identified,revealing evidence of inter-regional clonal spread,notably among 9 K.pneumoniae ST3393.Phylogenetic analysis revealed the presence of two K.pneumoniae ST5 closely resembling hypervirulent K.pneumoniae from Jiangsu.Importantly,12 isolates were capable of transferring tigecycline resistance to Escherichia coli J53.Further plasmid analysis showed that the tet(X4)-harboring plasmids in K.pneumoniae could be classified into four types,primarily belonging to the IncFIA(HI1)/HI1A/HI1B hybrid plasmid(n=16)and IncFII plasmid(n=7),which significantly contributed to the cross-species dissemination of tet(X4).In summary,this study highlights the prevalence of MDR tet(X4)-positive K.pneumoniae in Chengdu,driven predominantly by clonal expansion and plasmid-mediated horizontal gene transfer.These findings emphasize the importance of contin-uous surveillance of tet(X4)-positive K.pneumoniae in raw meat and the implementation of effective measures to control their spread.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB29010000)the External Cooperation Program of CAS(153211KYSB20160001).
文摘He and his colleagues[1]reported identification of the mobile resistance genes tet(X3)and tet(X4)on conjugative plasmids in Enterobacteriaceae and Acinetobacter isolated in China recently published in Nature Microbiology.They noted that both tet(X3)and tet(X4)can confer resistance to tigecycline and the newly FDA-approved eravacycline and omadacyclin,which are last-resort antibiotics used to treat multi-drug-resistant(MDR)bacterial infections.Our previous report[2]revealed that live poultry market(LPM)is a huge antibiotic resistance gene(ARG)reservoir,including the mobile colistin resistance(mcr)genes,mcr-1,mcr-3,mcr-4 and mcr-5.Large-scale metagenomic data screening showed that tigecycline resistance gene tet(X3)was widespread in poultry faecal samples collected from China LPMs,whereas it has not been detected in human(n=2019)gut microbiomes[3],which suggested that tet(X3)is previously confined to animal guts or animal-derived bacteria.
基金This study was supported by the Major Program of National Natural Science Foundation of China(81991534)the Major State Basic Research Development Program(2018YFC1603803)the National Key Research and Development Program of China(grant number:2018YFC1603900).
文摘The emergence and spread of plasmid-mediated tigecycline resistance genes have attracted extensive attention worldwide.We investigated the distribution of mobile tigecycline resistance genes in Salmonella genomes generated by both our laboratory and public bacterial genomes downloaded from the NCBI GenBank.The tet(X4)-positive strains were subjected to susceptibility testing and conjugation assays.The genetic features of the tet(X4)-bearing plasmid sequence were analyzed.Here,we report the identification of the plasmid-mediated tigecycline resistance gene tet(X4)in a conjugative plasmid of the Salmonella enterica serovar Llandoff strain SH16G3606,isolated from a man in China in 2016,the first reported serovar Llandoff in China as a novel sequence type ST8300.The tet(X4)-mediated resistance phenotype was successfully transferred from the Salmonella Llandoff strain into Escherichia coli J53,resulting in a 32-fold increase in the minimal inhibitory concentration of tigecycline.The tet(X4)gene was located between two copies of ISCR2 in the plasmid pSal21GXH-tetX4.To our knowledge,this is the first report of the plasmid-mediated tigecycline resistance gene tet(X4)in a Salmonella Llandoff strain isolated from a human stool sample in China.In addition,our findings demonstrated that a total of 171 isolates are carrying tet(X)-like genes distributed in 21 countries or areas across 6 continents,posing a serious threat to humans and public health.Overall,our timely discovery of the recent emergence of the tet(X4)gene in Salmonella isolates and other Enterobacteriaceae bacteria species supports the need for rapid surveillance to prevent the tet(X)-like gene from spreading.
基金This work was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(CAS,XDB29010202)the External Cooperation Program of CAS(153211KYSB20160001).
文摘The emergence of mobile Tigecycline-resistant tet(X3)and tet(X4)is believed to be a global threat to public health.Here,we investigated the prevalence of tet(X3)and tet(X4)in our metagenomic data of migratory birds.While tet(X4)was not identified in our samples,tet(X3)was found in two gut microbiomes of bird fecal samples,with 100%amino acid identity of sites 150–387.These results suggest that tet(X3)has been spreading into the environment for a long period of time and that there is an urgent need to control its further transmission.
文摘上调基因4(up-regulated gene-4,URG4)是受乙肝病毒X蛋白(hepatitis B virus X protein,HBx)激活的下游基因之一,最初在转染HBx的HepG2细胞中被克隆,因其上调细胞增殖效应而得名。研究发现,URG4在HBx转染后的HepG2细胞中表达明显增加,同时细胞生长加速,存活率提高,表明URG4与乙肝病毒相关的肝细胞癌发生可能相关。近年来,人们发现URG4不仅在肝癌细胞中高表达,还与胃癌、骨肉瘤、非小细胞肺癌、神经母细胞瘤等多种癌症相关。本文结合近年来对URG4的研究成果,包括URG4基因及其蛋白质的结构与功能,URG4在癌症发生发展中的作用,以及在癌症早期诊断和预后中的意义进行综述,可望为后续深入地开展URG4与癌症的研究提供参考。
