Inter-species geographic signatures for tracing horizontal gene transfer and long-term persistence of carbapenem resistance.

Inter-species geographic signatures for tracing horizontal gene transfer and long-term persistence of carbapenem resistance.
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DOI:
10.1186/s13073-022-01040-y
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发表时间:
2022-04-05
期刊:
影响因子:
12.3
通讯作者:
Earl AM
Earl AM
中科院分区:
生物学1区
文献类型:
--
作者:
Salamzade R;Manson AL;Walker BJ;Brennan-Krohn T;Worby CJ;Ma P;He LL;Shea TP;Qu J;Chapman SB;Howe W;Young SK;Wurster JI;Delaney ML;Kanjilal S;Onderdonk AB;Bittencourt CE;Gussin GM;Kim D;Peterson EM;Ferraro MJ;Hooper DC;Shenoy ES;Cuomo CA;Cosimi LA;Huang SS;Kirby JE;Pierce VM;Bhattacharyya RP;Earl AM

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Carbapenem-resistant Enterobacterales (CRE) are an urgent global health threat. Inferring the dynamics of local CRE dissemination is currently limited by our inability to confidently trace the spread of resistance determinants to unrelated bacterial hosts. Whole-genome sequence comparison is useful for identifying CRE clonal transmission and outbreaks, but high-frequency horizontal gene transfer (HGT) of carbapenem resistance genes and subsequent genome rearrangement complicate tracing the local persistence and mobilization of these genes across organisms. To overcome this limitation, we developed a new approach to identify recent HGT of large, near-identical plasmid segments across species boundaries, which also allowed us to overcome technical challenges with genome assembly. We applied this to complete and near-complete genome assemblies to examine the local spread of CRE in a systematic, prospective collection of all CRE, as well as time- and species-matched carbapenem-susceptible Enterobacterales, isolated from patients from four US hospitals over nearly 5 years. Our CRE collection comprised a diverse range of species, lineages, and carbapenem resistance mechanisms, many of which were encoded on a variety of promiscuous plasmid types. We found and quantified rearrangement, persistence, and repeated transfer of plasmid segments, including those harboring carbapenemases, between organisms over multiple years. Some plasmid segments were found to be strongly associated with specific locales, thus representing geographic signatures that make it possible to trace recent and localized HGT events. Functional analysis of these signatures revealed genes commonly found in plasmids of nosocomial pathogens, such as functions required for plasmid retention and spread, as well survival against a variety of antibiotic and antiseptics common to the hospital environment. Collectively, the framework we developed provides a clearer, high-resolution picture of the epidemiology of antibiotic resistance importation, spread, and persistence in patients and healthcare networks. The online version contains supplementary material available at 10.1186/s13073-022-01040-y.
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