Blankenship, H. M. | Search bioRxiv

bioRxiv2025

Tracking blaKPC Plasmid Dissemination within and between Enterobacterales across Michigan Over a Decade

AbstractblaKPC is endemic among Enterobacterales in the USA. While present on diverse plasmids, blaKPC 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 blaKPC 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 blaKPC 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 blaKPC 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. ImportanceThis 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.

genomics↗

bioRxiv2024

Intrapartum antibiotic prophylaxis selects for mutators in group B streptococci among persistently colonized patients

Through vaginal colonization, GBS causes severe outcomes including neonatal sepsis and meningitis. Although intrapartum antibiotic prophylaxis (IAP) has reduced neonatal disease rates, persistent GBS colonization has been observed in patients following prophylaxis. To determine whether IAP selects for genomic signatures that enhance GBS survival and persistence, a pangenome analysis was performed on 97 isolates from 58 participants before (prenatal) and after (postpartum) IAP/childbirth. Thirty-one of the 34 paired strains from participants with persistent colonization clustered together in the core gene phylogeny, suggesting that the strains recovered at the postpartum sampling were highly similar to those recovered at the prenatal visit. A core-gene mutation analysis identified mutations in 74% (n=23) of the 31 postpartum genomes when compared to the prenatal strains of the same multilocus sequence type recovered from the same individuals. Several strains had acquired mutations in the same colonization-associated genes, though two postpartum strains accounted for most of the mutations. These two outliers were classified as mutators based on high mutation rates and mutations within DNA repair system genes. Increased biofilm production was observed in half of the postpartum strains relative to the prenatal strains, which is supported by the presence of point mutations in genes associated with adherence. Together, these findings suggest that antibiotics may impose a selective pressure on GBS that selects for mutations and phenotypes that promote adaptation and survival in vivo. Enhanced survival in the genitourinary tract can lead to persistent colonization, increasing the likelihood of invasive disease in subsequent pregnancies and in newborns following IAP.

evolutionary biology↗