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水平基因转移在流感嗜血杆菌多药耐药发展中的作用。

Role of Horizontal Gene Transfer in the Development of Multidrug Resistance in Haemophilus influenzae.

机构信息

Norwegian National Advisory Unit on Detection of Antimicrobial Resistance, Department of Microbiology and Infection Control, University Hospital of North-Norway, Tromsø, Norway

Research Group for Host-Microbe Interactions, Department of Medical Biology, Faculty of Health Sciences, University of Tromsø (UiT)-The Arctic University of Norway, Tromsø, Norway.

出版信息

mSphere. 2020 Jan 29;5(1):e00969-19. doi: 10.1128/mSphere.00969-19.

DOI:10.1128/mSphere.00969-19
PMID:31996416
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6992377/
Abstract

colonizes the respiratory tract in humans and causes both invasive and noninvasive infections. Resistance to extended-spectrum cephalosporins in is rare in Europe. In this study, we defined acquired resistance gene loci and mutations in multidrug-resistant (MDR) and/or PBP3-mediated beta-lactam-resistant (rPBP3) strains, intending to understand the mode of spread of antibiotic resistance determinants in this species. Horizontal transfer of mobile genetic elements and transformation with resistance-conferring alleles were contributory. We found one small plasmid and three novel integrative conjugative elements (ICEs) which carry different combinations of resistance genes. Demonstration of transfer and/or ICE circular forms showed that the ICEs are functional. Two extensively MDR genetically unrelated strains (F and G) from the same geographical region shared an identical novel MDR ICE (Tn) harboring , -like, and (B). The first Nordic case of MDR septicemia, strain 0, originating from the same geographical area as these strains, had a similar resistance pattern but contained another ICE [Tn with , and (B)] with an overall structure quite similar to that of Tn Comparison of the complete genes among rPBP3 strains revealed that the entire gene or certain regions of it are identical in genetically unrelated strains, indicating horizontal gene transfer. Our findings illustrate that is capable of acquiring resistance against a wide range of commonly used antibiotics through horizontal gene transfer, in terms of conjugative transfer of ICEs and transformation of chromosomal genes. colonizes the respiratory tract in humans and causes both invasive and noninvasive infections. As a threat to treatment, resistance against critically important antibiotics is on the rise in Identifying mechanisms for horizontal acquisition of resistance genes is important to understand how multidrug resistance develops. The present study explores the antimicrobial resistance genes and their context in beta-lactam-resistant with coresistance to up to four non-beta-lactam groups. The results reveal that this organism is capable of acquiring resistance to a wide range of commonly used antibiotics through conjugative transfer of mobile genetic elements and transformation of chromosomal genes, resulting in mosaic genes with a broader resistance spectrum. Strains with chromosomally mediated resistance to extended-spectrum cephalosporins, co-trimoxazole, and quinolones combined with mobile genetic elements carrying genes mediating resistance to ampicillin, tetracyclines, and chloramphenicol have been reported, and further dissemination of such strains represents a particular concern.

摘要

定植于人类的呼吸道,引起侵袭性和非侵袭性感染。在欧洲,对扩展谱头孢菌素的耐药性在 中罕见。在这项研究中,我们定义了获得性耐药基因座和 突变在多药耐药(MDR)和/或 PBP3 介导的β-内酰胺耐药(rPBP3) 株中,旨在了解该物种中抗生素耐药决定因素的传播方式。移动遗传元件的水平转移和携带耐药基因的转化是有贡献的。我们发现了一个小质粒和三个新的整合性 conjugative 元件(ICEs),它们携带不同组合的耐药基因。转移和/或 ICE 环状形式的证明表明 ICEs是功能性的。来自同一地理区域的两个广泛 MDR 遗传上无关的 株(F 和 G)共享一个携带 、-样和(B)的相同新型 MDR ICE(Tn)。来自同一地理区域的首例北欧 MDR 败血症 0 株,具有相似的耐药模式,但含有另一个 ICE [Tn 携带 、 和(B)],整体结构与 Tn 非常相似。rPBP3 株之间的完整 基因比较表明,遗传上无关的株中整个基因或其某些区域是相同的,表明存在水平基因转移。我们的研究结果表明, 能够通过水平基因转移获得对广泛使用的抗生素的耐药性,包括 ICE 的共轭转移和染色体基因的转化。 定植于人类的呼吸道,引起侵袭性和非侵袭性感染。作为治疗的威胁,对重要抗生素的耐药性在 中呈上升趋势。确定水平获得耐药基因的机制对于了解多药耐药性的发展非常重要。本研究探讨了β-内酰胺耐药 中与核心耐药性至多达四个非β-内酰胺组相关的抗生素耐药基因及其结构。结果表明,该生物体能够通过移动遗传元件的共轭转移和染色体基因的转化获得对广泛使用的抗生素的耐药性,从而产生具有更广泛耐药谱的镶嵌基因。已经报道了对扩展谱头孢菌素、复方新诺明和喹诺酮类药物具有染色体介导耐药性的菌株,同时携带介导对氨苄西林、四环素和氯霉素耐药性的基因的移动遗传元件,此类菌株的进一步传播尤其令人担忧。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84a7/6992377/6e06423f4d30/mSphere.00969-19-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84a7/6992377/68e92fa71e0e/mSphere.00969-19-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84a7/6992377/b8b4908bf626/mSphere.00969-19-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84a7/6992377/71203db0cb72/mSphere.00969-19-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84a7/6992377/6abfe261dd4f/mSphere.00969-19-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84a7/6992377/6e06423f4d30/mSphere.00969-19-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84a7/6992377/68e92fa71e0e/mSphere.00969-19-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84a7/6992377/b8b4908bf626/mSphere.00969-19-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84a7/6992377/71203db0cb72/mSphere.00969-19-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84a7/6992377/6abfe261dd4f/mSphere.00969-19-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84a7/6992377/6e06423f4d30/mSphere.00969-19-f0005.jpg

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