# Comparative analysis of colonization and survival strategies of regionally predominant LA-MRSA clones ST398 and ST9

## TL;DR

This study compares the colonization and survival strategies of two LA-MRSA clones, ST398 and ST9, revealing why ST398 may become dominant in China as antibiotic use regulations tighten.

## Contribution

The study identifies distinct metabolic and colonization strategies of ST398 and ST9 LA-MRSA clones and links ST9's prevalence in China to antibiotic resistance.

## Key findings

- ST398 strains show superior colonization and resistance to macrophage-mediated killing compared to ST9.
- ST398 prioritizes genome repair and amino acid metabolism, while ST9 focuses on carbohydrate metabolism.
- Chinese ST9 isolates carry multiple resistance genes, suggesting their prevalence is driven by antimicrobial selection pressure.

## Abstract

Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) displays distinct geographical distribution patterns, with ST398 predominating in Europe and ST9 being the dominant lineage in Asia, particularly China. However, the mechanisms underlying these differences remain poorly understood. In this study, we evaluated the cell adhesion capacity, anti-phagocytic properties, and porcine nasal colonization potential of ST9 and ST398 strains isolated from China and Germany. Colonization dynamics and characteristics were further explored using 16S rRNA gene sequencing and metatranscriptomic analysis. Our findings revealed that LA-MRSA ST398 strains exhibited superior colonization capabilities, including enhanced cell adhesion, increased resistance to macrophage-mediated killing, and a stronger impact on nasal microbiota stability. Transcriptomic analyses during colonization indicated that ST398 strains prioritized pathways related to genome repair and amino acid metabolism, whereas ST9 strains, particularly those isolated from China, focused on carbohydrate metabolism. Although ST9 strains showed relatively weaker colonization capacity, the epidemic Chinese ST9 isolates carried multiple resistance genes [fexA, tet(L), and aadE-spw-lsa(E)-lnu(B)], exhibiting broad resistance to clinically important antibiotics including tylosin, florfenicol, and tetracyclines. This suggests that their prevalence in China may be maintained through antimicrobial selection pressure. With the implementation of stricter antibiotic use regulations in Chinese livestock production, ST398, due to its robust colonization potential, is likely to replace ST9 as the dominant LA-MRSA clone gradually.

Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) is a significant public health concern due to its zoonotic potential and resistance to antimicrobial agents. Despite its global presence, the geographical dominance of specific clones, such as ST398 in Europe and ST9 in Asia, remains poorly understood. This study sheds light on the distinct colonization strategies and metabolic adaptations of these LA-MRSA lineages. By demonstrating the superior colonization abilities and metabolic versatility of ST398 compared to ST9, we speculate that changes in antimicrobial usage policies may drive a shift in the dominance of LA-MRSA clones in China’s livestock industry. These insights provide valuable guidance for managing LA-MRSA transmission and developing effective intervention strategies to mitigate its impact on animal and human health.