全球临床病原体中移动遗传元件及其与抗生素抗性基因的关联研究。
Investigation of mobile genetic elements and their association with antibiotic resistance genes in clinical pathogens worldwide.
作者信息
Johansson Markus H K, Petersen Thomas N, Nag Sidsel, Lagermann Timmie M R, Birkedahl Laura E K, Tafaj Silva, Bradbury Susan, Collignon Peter, Daley Denise, Dougnon Victorien, Fabiyi Kafayath, Coulibaly Boubacar, Dembélé Réné, Magloire Natama, Ouindgueta Isidore J, Hossain Zenat Z, Begoum Anowara, Donchev Deyan, Diggle Mathew, Turnbull LeeAnn, Lévesque Simon, Berlinger Livia, Søgaard Kirstine K, Guevara Paula D, Duarte Carolina, Maikanti Panagiota, Amlerova Jana, Drevinek Pavel, Tkadlec Jan, Dilas Milica, Kaasch Achim, Westh Henrik T, Bachtarzi Mohamed A, Amhis Wahiba, Salazar Carolina E S, Villacis José E, Lúzon Mária A D, Palau Dàmaris B, Duployez Claire, Paluche Maxime, Asante-Sefa Solomon, Møller Mie, Ip Margaret, Mareković Ivana, Pál-Sonnevend Agnes, Cocuzza Clementiza E, Dambrauskiene Asta, Macanze Alexandre, Cossa Anelsio, Mandomando Inácio, Nwajiobi-Princewill Philip, Okeke Iruka N, Kehinde Aderemi O, Adebiyi Ini, Akintayo Ifeoluwa, Popoola Oluwafemi, Onipede Anthony, Blomfeldt Anita, Nyquist Nora E, Bocker Kiri, Ussher James, Ali Amjad, Ullah Nimat, Khan Habibullah, Gustafson Natalie W, Jarrar Ikhlas, Al-Hamad Arif, Luvira Viravarn, Paveenkittiporn Wantana, Baran Irmak, Mwansa James C L, Sikakwa Linda, Yamba Kaunda, Aarestrup Frank M
机构信息
National Food Institute, Technical University of Denmark, Kgs. Lyngby, Denmark.
Microbiology Department, University Hospital "Shefqet Ndroqi", Tirana, Albania.
出版信息
PLoS One. 2025 Aug 18;20(8):e0330304. doi: 10.1371/journal.pone.0330304. eCollection 2025.
OBJECTIVES
Antimicrobial-resistant bacteria are a major global health threat. Mobile genetic elements (MGEs) have been crucial for spreading resistance to new bacterial species, including human pathogens. Understanding how MGEs promote resistance could be essential for prevention. Here we present an investigation of MGEs and their association with resistance genes in pathogenic bacteria collected from 59 diagnostic units during 2020, representing a snapshot of clinical infections from 35 counties worldwide.
METHODS
We analysed 3,095 whole-genome sequenced clinical bacterial isolates from over 100 species to study the relationship between resistance genes and MGEs. The mobiliome of Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, and Klebsiella pneumoniae were further examined for geographic differences, as these species were prevalent in all countries. Genes potentially mobilized by MGEs were identified by finding DNA segments containing MGEs and ARGs preserved in multiple species. Network analysis was used to investigate potential MGE interactions, host range, and transmission pathways.
RESULTS
The prevalence and diversity of MGEs and resistance genes varied among species, with E. coli and S. aureus carrying more diverse elements. MGE composition differed between bacterial lineages, indicating strong vertical inheritance. 102 MGEs associated with resistance were found in multiple species, and four of these elements seemed to be highly transmissible as they were found in different phyla. We identified 21 genomic regions containing resistance genes potentially mobilized by MGEs, highlighting their importance in transmitting genes to clinically significant bacteria.
CONCLUSION
Resistance genes are spread through various MGEs, including plasmids and transposons. Our findings suggest that multiple factors influence MGE prevalence and their transposability, thereby shaping the MGE population and transmission pathways. Some MGEs have a wider host range, which could make them more important for mobilizing genes. We also identified 103 resistance genes potentially mobilised by MGEs, which could increase their transmissibility to unrelated bacteria.
目的
耐抗菌药物细菌是全球主要的健康威胁。移动遗传元件（MGEs）对于耐药性传播到新的细菌物种（包括人类病原体）起着关键作用。了解MGEs如何促进耐药性对于预防可能至关重要。在此，我们展示了一项对2020年从59个诊断单位收集的病原菌中MGEs及其与耐药基因关联的调查，这些病原菌代表了来自全球35个县的临床感染情况。
方法
我们分析了来自100多个物种的3095株全基因组测序临床细菌分离株，以研究耐药基因与MGEs之间的关系。由于金黄色葡萄球菌、粪肠球菌、大肠杆菌和肺炎克雷伯菌在所有国家都很普遍，因此进一步检查了它们的可移动基因组的地理差异。通过寻找包含MGEs和在多个物种中保留的抗菌耐药基因（ARGs）的DNA片段，确定了可能由MGEs移动的基因。网络分析用于研究潜在的MGE相互作用、宿主范围和传播途径。
结果
MGEs和耐药基因的流行率和多样性因物种而异，大肠杆菌和金黄色葡萄球菌携带更多样化的元件。细菌谱系之间的MGE组成不同，表明有很强的垂直遗传。在多个物种中发现了102个与耐药性相关的MGEs，其中有四个元件似乎具有高度可传播性，因为它们存在于不同的门中。我们确定了21个包含可能由MGEs移动的耐药基因的基因组区域，突出了它们在将基因传递给具有临床意义的细菌方面的重要性。
结论
耐药基因通过包括质粒和转座子在内的各种MGEs传播。我们的研究结果表明，多种因素影响MGEs的流行率及其转座能力，从而塑造了MGE群体和传播途径。一些MGEs具有更广泛的宿主范围，这可能使它们在移动基因方面更为重要。我们还确定了103个可能由MGEs移动的耐药基因，这可能会增加它们向无关细菌的传播能力。
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