# Reduced MGE burden, virulence optimization, and acid stress tolerance shape the clonal succession of MRSA ST59

## TL;DR

MRSA ST59 outcompetes ST239 in China due to reduced resistance, optimized virulence, and better acid tolerance.

## Contribution

Identifies evolutionary and functional traits enabling ST59's epidemiological dominance over ST239.

## Key findings

- ST59 has reduced MGE burden and retains key virulence genes, unlike ST239.
- Deletions in chp and sraP impair ST59's survival and adhesion, but it shows enhanced acid tolerance.
- ST239's decline is linked to multidrug resistance costs and genome degradation.

## Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) ST59 clone has replaced the historically dominant ST239 in China. However, the mechanisms behind this shift remain elusive. Phylogenetic analysis revealed divergent evolutionary trajectories: ST239 emerged via interlineage recombination and accumulated extensive resistance and genome degradation, whereas ST59 followed a more conserved, recombination-sparse path marked by reduced mobile genetic element (MGE) burden and retention of key virulence–associated MGEs. ST239’s decline was attributed to the fitness costs of multidrug resistance, widespread pseudogenization, and a closed pan-genome. Furthermore, ST59 exhibited enhanced virulence. Two key virulence determinants were identified: deletion of chp impaired survival in whole blood and neutrophil cocultures by disrupting C5a-mediated chemotaxis; sraP deletion reduced epithelial adhesion, nasal colonization, and systemic virulence. ST59 also demonstrated superior acid tolerance, linked to transcriptomic activation of transport and metabolic pathways. Our findings highlight that the epidemiological success of clones requires a balance of reduced resistance, targeted virulence, and environmental adaptability.

Epidemiological success of MRSA ST59 reflects reduced resistance burden, targeted virulence, and enhanced environmental tolerance.