Characterization of a novel gene, Lsa(F), conferring resistance to pleuromutilins, lincosamides and streptogramin A in Streptococcus parasuis

Transferable antimicrobial resistance poses significant threats to public health. This issue is further exacerbated by Lsa homolog-mediated resistance to pleuromutilins, lincosamides, and streptogramin A (PLS A ). This study aimed to characterize a novel PLS A resistance gene, designated Lsa(F), identified in Streptococcus parasuis . The Lsa(F) protein exhibits 41.9–58.7% sequence identity with known Lsa variants and shares structural features typical of the F lineage of the ATP-binding cassette (ABC) protein superfamily that confers ribosome protection. Functional expression of Lsa(F) in Streptococcus suis and Staphylococcus aureus confers resistance to PLS A . Although the prevalence of the Lsa(F) gene among S . parasuis isolates was found to be relatively low, database analyses revealed that this gene is primarily present in Streptococcus and Lactococcus species. In Streptococcus , the Lsa(F) gene is predominantly associated with various mobile genetic elements (MGEs), including plasmids, integrative and conjugative elements (ICE), and ICE-derived elements; in Lactococcus , it is primarily located on plasmids and at a specific chromosomal locus. Examination of the genetic context analysis identified the insertion sequence IS Lll1 downstream of Lsa(F) on almost all chromosomal MGEs and plasmids, suggesting a potential mechanism facilitating its movement. Notably, our results indicate that the Lsa(F) gene can be transferred from S. parasuis to Streptococcus suis , highlighting a risk of its spread to other pathogens. Therefore, it is necessary to enhance surveillance and epidemiological monitoring of the Lsa(F) gene to reduce the potential public health risks associated with its spread.