Multilocus sequence type-dependent activity of human and animal cathelicidins against community-, hospital-, and livestock-associated methicillin-resistant Staphylococcus aureus isolates

Sequence type (ST) 5 methicillin-resistant Staphylococcus aureus (MRSA) with staphylococcal cassette chromosome mec (SCCmec) type II (ST5-MRSA-II) and ST72-MRSA-IV represent the most significant genotypes for healthcare- (HA) and community-associated (CA) MRSA in Korea, respectively. In addition to the human-type MRSA strains, the prevalence of livestock-associated (LA) MRSA clonal lineages, such as ST541 and ST398 LA-MRSA-V in pigs and ST692 LA-MRSA-V and ST188 LA-MRSA-IV in chickens, has recently been found. In this study, clonotype-specific resistance profiles to cathelicidins derived from humans (LL-37), pigs (PMAP-36), and chickens (CATH-2) were examined using six different ST groups of MRSA strains: ST5 HA-MRSA-II, ST72 CA-MRSA-IV, ST398 LA-MRSA-V, ST541 LA-MRSA-V, ST188 LA-MRSA-IV, and ST692 LA-MRSA-V. Phenotypic characteristics often involved in cathelicidin resistance, such as net surface positive charge, carotenoid production, and hydrogen peroxide susceptibility were also determined in the MRSA strains. Human- and animal-type MRSA strains exhibited clonotype-specific resistance profiles to LL-37, PMAP-36, or CATH-2, indicating the potential role of cathelicidin resistance in the adaptation and colonization of human and animal hosts. The ST5 HA-MRSA isolates showed enhanced resistance to all three cathelicidins and hydrogen peroxide than ST72 CA-MRSA isolates by implementing increased surface positive charge and carotenoid production. In contrast, LA-MRSA strains employed mechanisms independent of surface charge regulation and carotenoid production for cathelicidin resistance. These results suggest that human- and livestock-derived MRSA strains use different strategies to counteract the bactericidal action of cathelicidins during the colonization of their respective host species.