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

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.