Genetic Factors Associated with Increased Host Defense Antimicrobial Peptide Resistance in Sequence Type 5 Healthcare-Associated MRSA Clinical Isolates

Sequence type (ST) 72 methicillin-resistant Staphylococcus aureus with staphylococcal cassette chromosome mec (SCCmec) type IV (ST72-MRSA-IV) and ST5-MRSA-II are the most significant lineages found in community-associated (CA) and healthcare-associated (HA) environments in Korea, respectively. ST5 HA-MRSA-II tend to display enhanced resistance to host defense-cationic antimicrobial peptides (HD-CAPs) compared to ST72 CA-MRSA-IV and ST72 livestock-associated (LA)-MRSA-IV due to mechanisms involving a higher surface positive charge. Thus, the present study explored the genetic factors contributing to the enhanced HD-CAP resistance phenotype in ST5 MRSA strains. The ST5 HA-MRSA-II strains displayed higher levels of mprF and dltABCD expression compared to the ST72 CA-/LA-MRSA-IV strains. The increase in expression of mprF and dltABCD in ST5 HA-MRSA-II strains was correlated with dysregulation of the upstream transcriptional regulator, graRS. However, single nucleotide polymorphisms (SNPs) within mprF and graRS ORFs were not involved in the enhanced surface positive charge or the altered expression of mprF/dltABCD.