Shankar Chaitra, Narayanan Dhatri Badri, Miihlbach Ashley, McNamara Sara, Brennan Brenda, Miles-Jay Arianna, Blankenship Heather, Bahr Auden, Snitkin Evan S
bioRxiv. 2025 Aug 22:2025.08.18.670900. doi: 10.1101/2025.08.18.670900.
is endemic among Enterobacterales in the USA. While present on diverse plasmids, burden is often associated with the clonal spread of multi-drug resistant (MDR) epidemic lineages. In this study we sought to determine the relative contributions of clonal spread and plasmid transfer to burden across Michigan healthcare facilities over a decade. To this end we performed whole-genome sequencing of 1,058 KPC-producing isolates collected from 47 Michigan healthcare facilities between 2013 and 2022, including long-read sequencing for 527 isolates to enable precise plasmid tracking. Analysis with MOB-suite identified 64 distinct KPC plasmid types ("secondary clusters"), with the AK975 broad-host range plasmid being the most prevalent, found in 27% of isolates, spanning 20 species and 92 sequence types. Among genomes with AK975, 30% were from epidemic and 70% non-epidemic lineages, highlighting its broad role in regional spread. Epidemic lineages of various species constituted 46% of the study population. Epidemic lineages differed in their primary plasmids, and even within epidemic lineages there were clonal expansions with distinct plasmids, including in some cases AK975. These findings highlight two patterns of KPC spread: transmission of epidemic lineages harboring broad-range and lineage-specific KPC plasmids; and broader spread of AK975 among diverse species. Traditional surveillance studies often focus on common MDR lineages, potentially overlooking rare species and lineages that mediate the spread of plasmid-borne antimicrobial resistance (AMR) genes. Here we show how longitudinal studies tracking plasmids across species are essential to understand the pathways leading to AMR infections in hospitals.
This decade-long longitudinal study highlights the persistence and spread of key KPC- carrying plasmid across multiple bacterial species in the region, including some uncommon ones. It also emphasizes the differences in KPC plasmids across lineages within the same species. While some lineages acquire multiple plasmids with resistance, they are unable to successfully maintain the plasmids. In contrast, clonal sub-populations of KPC-producing bacteria disseminate selected plasmids, establishing a stable host-plasmid combination. Comprehensive genomic surveillance that includes all pathogenic species and plasmids is crucial to understanding the regional transmission dynamics of plasmid-borne antimicrobial resistance (AMR). While outbreak studies define the blowup of a successful lineage and associated plasmids, longitudinal studies identify the reservoir-species and circulating plasmids in the context of plasmid- borne AMR.
在美国，肠杆菌科细菌中普遍存在。虽然存在于多种质粒上，但其负担通常与多重耐药（MDR）流行谱系的克隆传播有关。在本研究中，我们试图确定在十年间密歇根州各医疗机构中，克隆传播和质粒转移对其负担的相对贡献。为此，我们对2013年至2022年间从密歇根州47家医疗机构收集的1058株产KPC菌株进行了全基因组测序，其中527株进行了长读长测序以实现精确的质粒追踪。使用MOB-suite进行分析，鉴定出64种不同的KPC质粒类型（“二级簇”），其中AK975广宿主范围质粒最为普遍，在27%的菌株中发现，跨越20个物种和92个序列类型。在含有AK975的基因组中，30%来自流行谱系，70%来自非流行谱系，突出了其在区域传播中的广泛作用。不同物种的流行谱系占研究群体的46%。流行谱系的主要质粒不同，甚至在流行谱系内也有携带不同质粒的克隆扩增，包括在某些情况下的AK975。这些发现突出了KPC传播的两种模式：携带广宿主范围和谱系特异性KPC质粒的流行谱系的传播；以及AK975在不同物种中的更广泛传播。传统的监测研究通常集中在常见的MDR谱系上，可能会忽略介导质粒介导的抗菌药物耐药性（AMR）基因传播的罕见物种和谱系。在这里，我们展示了跨物种追踪质粒的纵向研究对于理解医院中导致AMR感染的途径至关重要。
这项长达十年的纵向研究突出了关键携带KPC质粒在该地区多种细菌物种中的持续存在和传播，包括一些不常见的物种。它还强调了同一物种内不同谱系间KPC质粒的差异。虽然一些谱系获得了多个耐药质粒，但它们无法成功维持这些质粒。相比之下，产KPC细菌的克隆亚群传播特定的质粒，建立了稳定的宿主 - 质粒组合。包括所有致病物种和质粒的全面基因组监测对于理解质粒介导的抗菌药物耐药性（AMR）的区域传播动态至关重要。虽然爆发研究定义了成功谱系和相关质粒的爆发，但纵向研究确定了质粒介导的AMR背景下的储存宿主物种和循环质粒。
