A New Class of Genetic Element, Staphylococcus Cassette Chromosome mec , Encodes Methicillin Resistance in Staphylococcus aureus

Abstract

We have previously shown that the methicillin-resistance gene mecA of Staphylococcus aureus strain N315 is localized within a large (52-kb) DNA cassette (designated the staphylococcal cassette chromosome mec [SCCmec]) inserted in the chromosome. By sequence determination of the entire DNA, we identified two novel genes (designated cassette chromosome recombinase genes [ccrA and ccrB]) encoding polypeptides having a partial homology to recombinases of the invertase/resolvase family. The open reading frames were found to catalyze precise excision of the SCCmec from the methicillin-resistant S. aureus chromosome and site-specific as well as orientation-specific integration of the SCCmec into the S. aureus chromosome when introduced into the cells as a recombinant multicopy plasmid. We propose that SCCmec driven by a novel set of recombinases represents a new family of staphylococcal genomic elements.Methicillin-resistant Staphylococcus aureus (MRSA) was first isolated in England in 1961 shortly after the development of methicillin, the first penicillinase-resistant semisynthetic penicillin (15). Since then, MRSA has become the most prevalent pathogen causing hospital infection throughout the world, and MRSA incidence is still increasing in many countries (1). MRSA is resistant to practically all ␤-lactam antibiotics, a class of antibiotics represented by penicillins and cephalosporins (3).The ␤-lactam resistance of MRSA is caused by the production of a novel penicillin-binding protein (PBP) designated PBP 2Ј (or PBP 2a), which, unlike the intrinsic set of PBPs (PBP 1 to 4) of S. aureus, has remarkably reduced binding affinities to ␤-lactam antibiotics (9,24,30). Despite the presence of otherwise inhibitory concentrations of ␤-lactam antibiotics, MRSA can continue cell wall synthesis solely depending upon the uninhibited activity of PBP 2Ј (21). PBP 2Ј is encoded by a mecA gene located on the chromosome of MRSA. In 1987, the mecA gene was cloned from a Japanese MRSA strain, and its sequence was determined (20,26). The mecA gene is widely distributed among S. aureus as well as coagulase-negative staphylococci (13, 28). Therefore, it has been speculated that the methicillin resistance determinant (mec determinant) is freely transmissible among staphylococcal species. However, with a detailed molecular epidemiological study, Kreiswirth et al. have proposed that MRSA originated from a single or two ancestral clones (16). This led to the view that the frequency of inter-or intraspecies transmission of mecA is a rather limited process and that mec transmission may not be due to specialized transmission machinery, such as a transposon.We have recently cloned and sequenced the entire chromosomal region surrounding the mecA gene, which is additionally present in the MRSA chromosome and is absent from the chromosome of methicillin-susceptible S. aureus (MSSA) (referred to herein as mecDNA), from a Japanese pre-MRSA strain, N315 (10). We identified the mecDNA-S. aureus chromosome junction points and the overall structure of me...

Prevalence and molecular characterization of methicillin resistance among Coagulase-negative Staphylococci at a tertiary care center

“…7 This may be due to the fact that heterogeneous expression of resistance varies more for MS-CoNS as compared to methicillin-sensitive Staphylococcus aureus (MSSA) and the subpopulation of resistant cells is smaller for MS-CoNS than for MSSA. 2 These reports confirm that expression of methicillin resistance is more variable for MS-CoNS and the detection of the mecA gene is important in interpreting methicillin susceptible staphylococci.…”

“…2 Staphylococcal chromosome cassette (SCC) mec is a resistance island present in the genome of methicillin-resistant isolates, where mec is the genetic element, that is responsible for resistance to methicillin. 2 mecA gene encodes for a particular penicillin-binding protein (PBP) called PBP2A, which has a low affinity for methicillin and most of the other b-lactam drugs and is thus responsible for the intrinsic resistance of these isolates to almost all b-lactams. Such multidrug-resistant strains are becoming a significant threat to public health.…”

“…Such multidrug-resistant strains are becoming a significant threat to public health. 2 This study was conducted with an aim to determine the prevalence of methicillin resistance among CoNS isolates by both phenotypic and genotypic methods.…”

Use of antimicrobials in veterinary medicine and mechanisms of resistance

“…Methicillinresistant Staphylococcus aureus (MRSA) isolates are resistant not only to all penicillins, but also to cephalosporins, carbapenems, and monobactams. The mecA gene which codes for β-lactam-resistant PBPs is located on a 52 kbp genetic element designated Staphylococcus cassette chromosome mec (SSCmec) [31]. PBPs which exhibit low affinity for β-lactams have also been detected in streptococci and enterococci [48].…”

Emergence of SCCmec Type IV as the Most Common Type of Methicillin-Resistant Staphylococcus aureus in a University Hospital

“…SCCmec is a mobile DNA element of 21-67 kb and is integrated into the chromosome of MRSA [1,2]. Hospital-associated MRSA (HA-MRSA) isolates are typically resistant to multiple antibiotics, negative for Panton-Valentine leukocidin (PVL) encoding genes and primarily harbor SCCmec types I, II, III, and rarely IV [1,3,4].…”