A new study has shown that the genetic background of recipient staphylococcal strains can have an important influence on whether or not the mobile genetic element responsible for methicillin resistance can jump between strains.
Methicillin-resistant Staphylococcus aureus (MRSA) are not only the most common cause of nosocomial infections, they are also significant community-acquired pathogens, particularly in children. S. aureus resistance to methicillin is conferred by the presence of a modified penicillin-binding transpeptidase, PBP2a, which is encoded by the mecA gene. mecA is carried on a mobile genetic element known as staphylococcal cassette chromosome mec (SCCmec), which is integrated into the S. aureus chromosome. There are 4 (and perhaps more) main classes of SCCmec and, despite the fact that SCCmec is mobile, its distribution is narrow and is principally restricted to just 5 clonal complexes worldwide.
What is the role of the genetic background of the staphylococcal host in this restricted clonal distribution? To answer this question, researchers at the University of California, San Francisco constructed two plamids: pYK20, containing the mecA gene alone, and pYK644, containing mecA and its repressors mecR1 and mecI. Analysis of PBP2a expression revealed that in all 'experienced' staphylococcal host strains — defined as methicillin-sensitive S. aureus (MSSA) strains created by the excision of SCCmec from the chromosome of MRSA strains — pYK20 was stably maintained. In naive staphylococcal host strains — MSSA strains that have never hosted mecA — pYK20 was unstable and PBP2a expression was heterogeneous and varied with the host genotype.
pYK644, by contrast, was stably maintained in naive hosts, implying that the mecA-associated regulatory genes can influence the clonal restriction of mecA acquisition. In most clinical MRSA isolates, the mecA regulatory genes are deleted and mecA is regulated by blaR1 and blaI, genes that are homologous to mecR1 and mecI, respectively and which also regulate blaZ, the gene encoding β-lactamase. Katayama and colleagues found that the bla regulatory regions did have a permissive effect on mecA acquisition in naive strains, although this effect was not as strong as that of the mec genes.
Horizontal transfer of the mec element has long been recognised as a major contributor to the evolution of MRSA strains, yet the clonal restriction of mecA distribution has always been puzzling. This work highlights the important contribution of the genetic background of the host staphylococcal strain to this process.
ORIGINAL RESEARCH PAPER
Katayama, Y. et al. Jumping the barrier to β-lactam resistance in Staphylococcus aureus. J. Bacteriol. 185, 5465–5472 (2003).
Enright, M. C. et al. The evolutionary history of methicillin-resistant Staphylococcus aureus (MRSA). Proc. Natl Acad. Sci. USA 99, 7687–7692 (2002).
Chambers, H. F. Solving staphylococcal resistance to β lactams. Trends Microbiol. 11, 145–148 (2003).
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Clarkson, S. Look before you leap. Nat Rev Microbiol 1, 90 (2003). https://doi.org/10.1038/nrmicro760