A pivotal event in the evolutionary path of methicillin-resistant Staphylococcus aureus (MRSA) is the acquisition of the staphylococcal cassette chromosome mec (SCCmec) element carrying the mecA gene, the determinant of methicillin resistance. Community-acquired (CA) MRSA is commonly associated with skin/soft tissue infections, and doxycycline is one of the drug choices for this purpose. Doxycycline resistance is associated with the acquisition of the tetK gene carried by the S. aureus plasmid pT181, which may also be integrated into SCCmec III and V. The aim of this study was to describe a novel SCCmec IV subtype (IVm) carrying tetK and reveal the genetic context of this element. The SCCmec sequence was obtained by whole-genome sequencing of the MRSA strain 2288 (ST1 CA-MRSA) and genomic analysis performed using different bioinformatics tools. A copy of pT181 was found to be integrated in the new SCCmec IVm of the strain 2288. The SCCmec IVm has high nucleotide identity (99%) with SCCmec IVa of the strain MW2, except for the J3 region, where the pT181 - carrying tetK gene - is inserted. Inverted repeats (IRs) flanking pT181 were found in this region, suggesting the occurrence of recombination events. The strain 2288 (spa type t125) shares most of the virulence attributes with MW2 (spa type t128), which is recognized in the past as a cause of severe infections in children in USA. The pattern of branching in the phylogenetic tree depicts a recent common ancestor shared by the 2228 strain and other MRSA from USA, including ERS410852, TCH70, CIG1835, CO-41, MW2, and USA400-0051, but none of them carried pT181. This study also showed that the tetK carried by SCCmec IVm is functional, determining resistance to doxycycline and tetracycline. The potential dissemination of the tetK and mecA genes in the same genetic event by the acquisition of this new SCCmec subtype is of concern for community infections.
Keywords: CA-MRSA; MRSAmec cassette; doxycycline resistance.