The bla and mec families of β-lactam resistance genes in the genera Macrococcus, Mammaliicoccus and Staphylococcus: an in-depth analysis with emphasis on Macrococcus

Abstract β-Lactamases (Bla) and low-affinity penicillin-binding proteins (PBP2A) are responsible for β-lactam resistance in the genera Macrococcus, Mammaliicoccus and Staphylococcus. These resistance mechanisms are in most species acquired through mobile genetic elements that carry a blaZ-like β-lactamase gene for penicillin resistance and/or a mec gene (mecA, mecB, mecC,mecD) encoding a PBP2A for resistance to virtually all classes of β-lactams. The mecA and mecC genes can be acquired through staphylococcal cassette chromosome mec (SCCmec) elements in Staphylococcus and Mammaliicoccus. The mecB and mecD genes are found in Macrococcus on SCCmec elements, as well as on unrelated mecD-carrying Macrococcus resistance islands (McRImecD) and large mecB-carrying plasmids. This review provides a phylogenetic overview of Macrococcus, Mammaliicoccus and Staphylococcus species and an in-depth analysis of the genetic structures carrying bla and mec genes in these genera. Native bla genes were detected in species belonging to the novobiocin-resistant Staphylococcus saprophyticus group and Mammaliicoccus. The evolutionary relatedness between Macrococcus and Mammaliicoccus is illustrated on the basis of a similar set of intrinsic PBPs, especially, the presence of a second class A PBP. The review further focuses on macrococcal elements carrying mecB and mecD, and compares them with structures present in Staphylococcus and Mammaliicoccus. It also discusses the different recombinases (ccr of SCCmec) and integrases (int of McRI) that contribute to the mobility of methicillin resistance genes, revealing Macrococcus as an important source for mobilization of antibiotic resistance genes within the family of Staphylococcaceae.