Trends in Microbiology
Volume 9, Issue 10, 1 October 2001, Pages 486-493
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Review
The emergence and evolution of methicillin-resistant Staphylococcus aureus

https://doi.org/10.1016/S0966-842X(01)02175-8Get rights and content

Abstract

Significant advances have been made in recent years in our understanding of how methicillin resistance is acquired by Staphylococcus aureus. Integration of a staphylococcal cassette chromosome mec (SCCmec) element into the chromosome converts drug-sensitive S. aureus into the notorious hospital pathogen methicilin-resistant S. aureus (MRSA), which is resistant to practically all β-lactam antibiotics. SCCmec is a novel class of mobile genetic element that is composed of the mec gene complex encoding methicillin resistance and the ccr gene complex that encodes recombinases responsible for its mobility. These elements also carry various resistance genes for non-β-lactam antibiotics. After acquiring an SCCmec element, MRSA undergoes several mutational events and evolves into the most difficult-to-treat pathogen in hospitals, against which all extant antibiotics including vancomycin are ineffective. Recent epidemiological data imply that MRSA has embarked on another evolutionary path as a community pathogen, as at least one novel SCCmec element seems to have been successful in converting S. aureus strains from the normal human flora into MRSA.

Section snippets

Integration of the SCCmec element into the S. aureus chromosome

In recent years, significant advances have been made in defining in simple genetic terms how MRSA arose. MRSA was ‘born’ when it acquired a large genetic element known as the staphylococcal cassette chromosome mec (SCCmec) 6, 7, 8 (Fig. 1). SCCmec is a 21–67 kb fragment of DNA that integrates in the chromosome of MRSA at a unique site (attBscc) located near the S. aureus origin of replication (Fig. 2). attBscc is found in an open reading frame (ORF) of unknown function, designated orfX, that is

Evolution towards high methicillin resistance

Pre-MRSA The acquisition of SCCmec is the first common genetic event for S. aureus to become fully β-lactam resistant. However, at least two more genetic events are involved in the evolution of clonotype-II-A MRSA, which is by far the most dominant MRSA in Japanese hospitals. This clone possesses a class A mec complex. Unlike the bla regulatory gene system (blaI-blaR1) for β-lactamase induction, the mec regulatory gene system (mecI-mecR1) involved in the regulation of mecA gene transcription

Evolution towards vancomycin resistance

Because of the limited space, only an outline of vancomycin resistance is given here; for more details see 14, 22, 25.

Acknowledgements

This work was supported by the Core University System Exchange Programme under the Japan Society for the Promotion of Science (JSPS), coordinated by the University of Tokyo Graduate School of Medicine and Mahidol University. The study was also partly supported by a Grant for International Health Cooperation Research (11C-4) from the Ministry of Health and Welfare.

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