The current view on betalactam resistance in Staphylococcus aureus

Abstract

The review presents the current view on the different resistance mechanisms of Staphylococcus aureus to beta-lactams, which are ones of the main antibiotics of choice for the treatment of staphylococcal infections. Currently, there are several mechanisms of resistance such as production of staphylococcal beta-lactamase (blaZ), which provides resistance to penicillins and aminopenicillins. Another one is the presence of an alternative penicillin-binding protein (PBP2a), which is the main marker of methicillinresistant S. aureus (MRSA), virtually providing resistance to all beta-lactams, with the exception of antiMRSA cephalosporins. Mutations in PBP2a contribute to the resistance to ceftaroline and ceftobiprol. Among the MRSA there are few exceptions with regards to the phenotypes called oxacillin-sensitive MRSA (OS-MRSA) which are susceptible to oxacillin despite the presence of the mecA encoding PBP2a. In addition, there are mec-independent pathways of beta-lactam resistance that could be found in S. aureus. In particular, mutations in the gdpP are associated with an increase in the intracellular concentration of c-diAMP messengers that promote resistance to beta-lactams, including anti-MRSA cephalosporins. Mutations in PBP4 or its promoter also contribute to the resistance. The mechanism of resistance to beta-lactams in mec-negative S. aureus (borderline oxacillin-resistant S. aureus, BORSA) is associated with the mutations in PBP1, PBP2, PBP3, and PBP4 or the overexpression of staphylococcal beta-lactamase. This review describes those and other phenotypes, the features of resistance mechanisms, clinical significance, as well as the possibilities for phenotypic detection.