# Evolutionary and Mobile Genetic Element Analysis of a Multidrug-Resistant ST398-MRSA-Vc Isolate from Ready-to-Eat Pork Products

## TL;DR

A multidrug-resistant ST398-MRSA-Vc isolate from pork products was analyzed to understand its genetic makeup and resistance mechanisms.

## Contribution

The study reveals the role of mobile genetic elements in the adaptation of ST398-MRSA-Vc to food environments and cross-host transmission.

## Key findings

- The isolate NPREF115 clustered with human and animal-derived ST398-MRSA-Vc isolates, suggesting shared ancestry.
- Genomic divergence was largely due to mobile genetic elements like SCCmec and Tn560 carrying resistance genes.
- NPREF115 contains a unique metabolic gene aiding survival in high-osmolarity food environments.

## Abstract

Background: Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) ST398 poses a significant zoonotic threat, largely due to its capacity to acquire and disseminate antimicrobial resistance through mobile genetic elements (MGEs). Ready-to-eat (RTE) foods may serve as critical interfaces for zoonotic spillover. However, genomic data on ST398-MRSA-Vc isolates from RTE foods remain scarce, leaving the characteristics of their MGEs largely unresolved. Methods: This study performed whole-genome sequencing and comparative genomic analysis of an ST398-MRSA-Vc isolate (NPREF115) from an RTE pork product in China. Using NPREF115 and 134 publicly available S. aureus genomes from diverse sources, we constructed a core genome phylogeny and conducted SNP and pangenome analyses, with a focus on MGEs. Results: Phylogenetic analysis revealed that our foodborne ST398-MRSA-Vc isolate clustered with human, Capra pyrenaica, bovine, and swine-derived ST398-MRSA-Vc isolates. SNP analysis indicated NPREF115 was most closely related to human clinical isolates (132 and 140 SNPs, respectively), consistent with shared ancestry rather than recent cross-host transmission. Genomic divergence was largely confined to MGEs, including SCCmec, prophages, genomic islands, and a chromosomally integrated Tn560 carrying the ant(9)-Ia-lsa(E)-lnu(B) multidrug resistance cluster. Notably, NPREF115 harbored a unique metabolic gene that may facilitate persistence in high-osmolarity food environments. Conclusions: The successful colonization of food by the ST398-MRSA-Vc isolate is likely associated with the acquisition of multiple MGEs harboring antimicrobial resistance genes. Transmission of ST398-MRSA-Vc between food, human, and livestock hosts was accompanied by changes in genes involved in metabolism. These findings underscore the importance of monitoring MGEs in genomic surveillance of foodborne MRSA.