Lixin Yan, Tingting Ma, Wen Wang, Zhen Cai, Hong Du, Zhongju Chen, Renru Han, Yan Guo, Gang Li, Wei Jia, Jia Tao
{"title":"中国耐替加环素和碳青霉烯肠杆菌科的流行病学和耐药机制：一项多中心基因组研究。","authors":"Lixin Yan, Tingting Ma, Wen Wang, Zhen Cai, Hong Du, Zhongju Chen, Renru Han, Yan Guo, Gang Li, Wei Jia, Jia Tao","doi":"10.3389/fmicb.2025.1582851","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>To elucidate the molecular epidemiology of tigecycline and carbapenem-resistant <i>Enterobacteriaceae</i> isolates and mechanisms of tigecycline resistance.</p><p><strong>Methods: </strong>We gathered 31 unduplicated strains of tigecycline-resistant <i>Enterobacteriaceae</i> from six hospitals nationwide. Antimicrobial susceptibility testing, phenotypic detection, and PCR identification were performed first, followed by homology analysis using MLST and PFGE. Conjugation transfer experiments using resistance gene plasmids were carried out, and the conjugates' growth curves were examined. All strains were sequenced using the Illumina HiSeq technology, and we identified a strain KP28 carrying a complete gene cluster <i>tmexCD2-toprJ2</i>. Then, its plasmid was further constructed using the PacBio platforms to complete the frame. The genetic connection of the <i>tmexCD2-toprJ2</i> gene cluster carried by KP28 was established using core genome analyses.</p><p><strong>Results: </strong>All 31 tigecycline-resistant <i>Enterobacteriaceae</i> strains (TG-CRE) were multidrug resistant. PFGE classified strains of CRKP, CRECL, and CRKAE into 16 distinct spectra, 6 distinct spectra, and 3 distinct spectra. MLST results showed a high concentration of ST11 in CRKP strains and a predominance of ST116 in CRECL strains, suggesting possible clonal transmission or selective dominance. The findings of the plasmid conjugation assay revealed that three strains expressing carbapenem resistance genes were effectively transmitted to the recipient cell <i>E. coli</i> EC600. WGS data revealed that these 31 strains include 79 resistance genes, with one strain (KP28) carrying the whole tigecycline resistance gene cluster, <i>tmexC2D2-toprJ2</i>. This resistance gene is contained in a large IncHI5 plasmid, which is difficult to transfer.</p><p><strong>Conclusion: </strong>The overall carriage rate of the <i>tmexC2D2-toprJ2</i> gene cluster was found to be low among the five Chinese hospitals investigated. Conversely, <i>tet</i>(A) mutations were present in most of the strains. Bacteria with the carbapenem resistance genes <i>bla</i> <sub>KPC</sub> and <i>bla</i> <sub>NDM</sub> are vulnerable to horizontal transmission. Increasing the risk of transmission of antibiotic-resistant genes.</p>","PeriodicalId":12466,"journal":{"name":"Frontiers in Microbiology","volume":"16 ","pages":"1582851"},"PeriodicalIF":4.0000,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12092438/pdf/","citationCount":"0","resultStr":"{\"title\":\"Epidemiology and resistance mechanisms of tigecycline- and carbapenem-resistant <i>Enterobacteriaceae</i> in China: a multicentre genome-based study.\",\"authors\":\"Lixin Yan, Tingting Ma, Wen Wang, Zhen Cai, Hong Du, Zhongju Chen, Renru Han, Yan Guo, Gang Li, Wei Jia, Jia Tao\",\"doi\":\"10.3389/fmicb.2025.1582851\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objectives: </strong>To elucidate the molecular epidemiology of tigecycline and carbapenem-resistant <i>Enterobacteriaceae</i> isolates and mechanisms of tigecycline resistance.</p><p><strong>Methods: </strong>We gathered 31 unduplicated strains of tigecycline-resistant <i>Enterobacteriaceae</i> from six hospitals nationwide. Antimicrobial susceptibility testing, phenotypic detection, and PCR identification were performed first, followed by homology analysis using MLST and PFGE. Conjugation transfer experiments using resistance gene plasmids were carried out, and the conjugates' growth curves were examined. All strains were sequenced using the Illumina HiSeq technology, and we identified a strain KP28 carrying a complete gene cluster <i>tmexCD2-toprJ2</i>. Then, its plasmid was further constructed using the PacBio platforms to complete the frame. The genetic connection of the <i>tmexCD2-toprJ2</i> gene cluster carried by KP28 was established using core genome analyses.</p><p><strong>Results: </strong>All 31 tigecycline-resistant <i>Enterobacteriaceae</i> strains (TG-CRE) were multidrug resistant. PFGE classified strains of CRKP, CRECL, and CRKAE into 16 distinct spectra, 6 distinct spectra, and 3 distinct spectra. MLST results showed a high concentration of ST11 in CRKP strains and a predominance of ST116 in CRECL strains, suggesting possible clonal transmission or selective dominance. The findings of the plasmid conjugation assay revealed that three strains expressing carbapenem resistance genes were effectively transmitted to the recipient cell <i>E. coli</i> EC600. WGS data revealed that these 31 strains include 79 resistance genes, with one strain (KP28) carrying the whole tigecycline resistance gene cluster, <i>tmexC2D2-toprJ2</i>. This resistance gene is contained in a large IncHI5 plasmid, which is difficult to transfer.</p><p><strong>Conclusion: </strong>The overall carriage rate of the <i>tmexC2D2-toprJ2</i> gene cluster was found to be low among the five Chinese hospitals investigated. Conversely, <i>tet</i>(A) mutations were present in most of the strains. Bacteria with the carbapenem resistance genes <i>bla</i> <sub>KPC</sub> and <i>bla</i> <sub>NDM</sub> are vulnerable to horizontal transmission. 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Epidemiology and resistance mechanisms of tigecycline- and carbapenem-resistant Enterobacteriaceae in China: a multicentre genome-based study.
Objectives: To elucidate the molecular epidemiology of tigecycline and carbapenem-resistant Enterobacteriaceae isolates and mechanisms of tigecycline resistance.
Methods: We gathered 31 unduplicated strains of tigecycline-resistant Enterobacteriaceae from six hospitals nationwide. Antimicrobial susceptibility testing, phenotypic detection, and PCR identification were performed first, followed by homology analysis using MLST and PFGE. Conjugation transfer experiments using resistance gene plasmids were carried out, and the conjugates' growth curves were examined. All strains were sequenced using the Illumina HiSeq technology, and we identified a strain KP28 carrying a complete gene cluster tmexCD2-toprJ2. Then, its plasmid was further constructed using the PacBio platforms to complete the frame. The genetic connection of the tmexCD2-toprJ2 gene cluster carried by KP28 was established using core genome analyses.
Results: All 31 tigecycline-resistant Enterobacteriaceae strains (TG-CRE) were multidrug resistant. PFGE classified strains of CRKP, CRECL, and CRKAE into 16 distinct spectra, 6 distinct spectra, and 3 distinct spectra. MLST results showed a high concentration of ST11 in CRKP strains and a predominance of ST116 in CRECL strains, suggesting possible clonal transmission or selective dominance. The findings of the plasmid conjugation assay revealed that three strains expressing carbapenem resistance genes were effectively transmitted to the recipient cell E. coli EC600. WGS data revealed that these 31 strains include 79 resistance genes, with one strain (KP28) carrying the whole tigecycline resistance gene cluster, tmexC2D2-toprJ2. This resistance gene is contained in a large IncHI5 plasmid, which is difficult to transfer.
Conclusion: The overall carriage rate of the tmexC2D2-toprJ2 gene cluster was found to be low among the five Chinese hospitals investigated. Conversely, tet(A) mutations were present in most of the strains. Bacteria with the carbapenem resistance genes blaKPC and blaNDM are vulnerable to horizontal transmission. Increasing the risk of transmission of antibiotic-resistant genes.
期刊介绍：
Frontiers in Microbiology is a leading journal in its field, publishing rigorously peer-reviewed research across the entire spectrum of microbiology. Field Chief Editor Martin G. Klotz at Washington State University is supported by an outstanding Editorial Board of international researchers. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
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