Development of Methicillin Resistance in Clinical Isolates of Staphylococcus sciuri by Transcriptional Activation of the mecA Homologue Native to the Species

Abstract

The ␤-lactam resistance gene mecA was acquired by Staphylococcus aureus from an extraspecies source. The search for the possible origin of this gene has led to the identification of a close structural homologue of mecA as a native gene in the animal species Staphylococcus sciuri. Surprisingly, the overwhelming majority of S. sciuri isolates were fully susceptible to ␤-lactam antibiotics in spite of the ubiquitous presence of the mecA homologue in the bacteria. We now describe two unusual S. sciuri strains isolated from humans-SS-37 and SS-41-that showed resistance to methicillin associated with high rates of transcription of the mecA homologue and production of a protein resembling penicillin binding protein 2a, the gene product of S. aureus mecA. In strain SS-37 increased transcription of the mecA homologue was related to insertion of an IS256 element upstream of the structural gene, and strain SS-41 had single nucleotide alterations in the promoter region of the mecA homologue which appear to be related to up-regulation of the rate of transcription. A third methicillin-resistant human isolate of S. sciuri that carries both the native mecA homologue and a methicillin-resistant S. aureus (MRSA) type mecA, strain K3, was now shown to be unstable in the absence of drug selection, causing the segregation of antibiotic-susceptible cells accompanied by the loss of the MRSA type mecA. These observations illustrate the remarkable variety of strategies available to bacteria for acquiring mechanisms of drug resistance in the in vivo environment.The cellular mechanism of broad-spectrum ␤-lactam antibiotic resistance, by which Staphylococcus aureus and other staphylococcal species are capable of withstanding the inhibitory effects of all ␤-lactam antibiotics, including the semisynthetic ones such as methicillin, is based on acquisition of the mecA gene, the product of which is penicillin binding protein 2a (PBP2a), a protein with greatly reduced affinity to this class of antibiotics (10). The resistance mechanism conferred by mecA has been studied extensively not only because of the importance of resistant strains in the clinical setting but also because of the intriguing features of the mechanism itself, which still holds many unanswered questions. One such question is the origin of the mecA determinant, known for a long time to be exogenous to S. aureus and to other clinically relevant staphylococci (1,5,9). In a search for the possible original source of mecA, we identified a genetic element closely related to the S. aureus mecA gene in the animal commensal species Staphylococcus sciuri, which is one of the most abundant staphylococcal species on our planet (12) and is only distantly related to S. aureus along taxonomic lines (21, 24). The broad range of S. sciuri biochemical activities, including the ability to use inorganic nitrogen salts as the sole source of nitrogen, is usually considered the reason for the wide range of host organisms and habitats of this bacterium, which include the skins of several animals as we...

Genetic characterization of antimicrobial resistance in coagulase-negative staphylococci from bovine mastitis milk

“…Alterations to the promoter region of mecA1 are necessary for high-level mecA1 expression and oxacillin resistance in Staph. sciuri (Wu et al, 2001(Wu et al, , 2005Couto et al, 2003). In our study, none of the Staph.…”

“…sciuri isolates are susceptible to β-lactam antimicrobials. However, alterations in the promoter regions of mecA1 upregulate mecA1 expression and confer methicillin resistance (Wu et al, 2001(Wu et al, , 2005Couto et al, 2003). Methicillin-resistant staphylococci are often also resistant to other classes of drugs such as aminoglycosides and macrolides (Woodford 2005).…”

Antimicrobial resistance: the example of Staphylococcus aureus

“…Couto et al (55) identified a mecA gene in a methicillin-sensitive Staphylococcus sciuri with 88% homology on the amino acid level to MRSA. Transduction of the S. sciuri mecA into an MSSA resulted in increased resistance to methicillin coupled with the detection of PBP2a (56). These studies therefore suggest one possible source of the mecA element in S. aureus.…”

Antibiotic Resistance in the Environment, with Particular Reference to MRSA

“…aureus (MSSA) homologue exists (Archer and Neimeyer, 1994) it has been suggested that it was transferred horizontally from a coagulase-negative staphylococcus (CoNS) such as S. sciuri (Couto et al, 1996;Couto et al, 2003). The conjugative transposon containing tetM (tetracycline resistance) has been suggested to pass between Clostridia and staphylococci (Ito et al, 2003), and empirical support for the movement of mobile elements between staphylococci and other low GC gram negative bacteria (Gill et al, 2005), and the potential transfer of vanA (vancomycin resistance) from Enterococcus faecalis to S. aureus (Weigel et al, 2003) lends weight to the possibility of a common gene pool available to many bacterial species (Hanssen et al, 2004).…”