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  • Review Article
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Waves of resistance: Staphylococcus aureus in the antibiotic era

Nature Reviews Microbiology volume 7, pages 629–641 (2009)Cite this article

Key Points

  • Staphylococcus aureus is notorious for its ability to become resistant to antibiotics. Antibiotic resistance in this organism has occurred in epidemic waves, beginning with the emergence of strains that were resistant to penicillin and progressing to the present pandemic of community-associated methicillin-resistant S. aureus (CA-MRSA). This article reviews the recent evolutionary history of drug-resistant strains of S. aureus.

  • We discuss the molecular epidemiology of the epidemics of penicillin- and methicillin-resistant strains of S. aureus that have occurred since 1940 and their common features.

  • The evolution of the mobile chromosome cassette element SCCmec, which carries mecA, the gene that determines resistance to methicillin and the entire class of β-lactam antibiotics, is also reviewed.

  • The clinical and molecular epidemiology of CA-MRSA is then discussed, along with the virulence determinants that are present in CA-MRSA strains and the possible genetic basis of the epidemicity and disease severity that is associated with these strains.

  • Finally, we look at antimicrobial therapy in the era of CA-MRSA.

Abstract

Staphylococcus aureus is notorious for its ability to become resistant to antibiotics. Infections that are caused by antibiotic-resistant strains often occur in epidemic waves that are initiated by one or a few successful clones. Methicillin-resistant S. aureus (MRSA) features prominently in these epidemics. Historically associated with hospitals and other health care settings, MRSA has now emerged as a widespread cause of community infections. Community or community-associated MRSA (CA-MRSA) can spread rapidly among healthy individuals. Outbreaks of CA-MRSA infections have been reported worldwide, and CA-MRSA strains are now epidemic in the United States. Here, we review the molecular epidemiology of the epidemic waves of penicillin- and methicillin-resistant strains of S. aureus that have occurred since 1940, with a focus on the clinical and molecular epidemiology of CA-MRSA.

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Figure 1: The four waves of antibiotic resistance in Staphylococcus aureus.
Figure 2: An example of a multilocus sequence typing scheme and the designation of clonal complexes.
Figure 3: Distribution of antibiotic-susceptible and -resistant Staphylococcus aureus among clonal complexes.
Figure 4: Comparison of the methicillin resistance cassettes that are typical of hospital- or community-acquired methicillin-resistant Staphylococcus aureus.

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Acknowledgements

F.R.D. is supported by the Intramural Research Program of the National Institute of Allergy and Infectious Disease (NIAID) and the National Institutes of Health (NIH) and H.F.C. is supported by the NIH, NIAID grant number R01 AI070289.

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Authors and Affiliations

  1. Division of Infectious Diseases, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, 94110, California, USA

    Henry F. Chambers

  2. Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th Street, Hamilton, 59840, Montana, USA

    Frank R. DeLeo

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DATABASES

Entrez Genome Project

MRSA strain COL

MRSA strain MW2

MRSA strain USA300

Staphylococcus aureus

Staphylococcus epidermidis

FURTHER INFORMATION

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SCCmec

Glossary

Necrotizing fasciitis

A rapidly progressive, tissue-destructive infection of the deep soft tissue and muscle, which spreads along the fibrous connective tissue that separates and binds muscles.

Necrotizing pneumonia

An infection of the lung, usually caused by bacteria, that produces death and destruction of the lung tissue and is often accompanied by abscess formation.

Panton–Valentine leukocidin

A bacteriophage-encoded, two-component, β-pore-forming toxin that integrates into the membranes of macrophages, monocytes and neutrophils and is cytolytic for these cells.

Phage type

An intraspecies strain, clone or type of bacterium that is differentiated and defined on the basis of its susceptibility to lysis by one or a panel of species-specific bacteriophages (viruses that propagate in bacterial cells).

Pulsed-field gel electrophoresis

A method for the separation of large fragments of DNA that is used in molecular epidemiology to visualize the bacterial strain-specific genome fingerprints that are generated by restriction digestion of whole genomes.

Multilocus sequence typing

An unambiguous procedure for characterizing isolates of bacterial species using the sequences of internal fragments of (usually) seven housekeeping genes. Approximately 450–500 bp internal fragments of each gene are used, as these can be accurately sequenced on both strands using an automated DNA sequencer.

SCCmec allotype

A variant of the chromosomal cassette (a mobile element in staphylococci) that encodes the gene (mecA) that is responsible for resistance to β-lactam antibiotics; specific allotypes are defined according to differences in the sequence or genetic organization of two regions, mecA and the ccr, which encodes the recombinase function that excises and integrates the cassette at a specific location in the staphylococcal chromosome.

Staphylokinase

A secreted 15.5 kDa fibrin-specific protein produced by S. aureus that forms a complex with plasminogen to generate plasmin, a proteolytic enzyme that cleaves fibrin.

Staphylococcal complement inhibitor

A secreted 9.8 kDa protein that inhibits the activation of human complement, thereby interfering with the phagocytosis and killing of staphylococci by neutrophils.

Staphylococcus aureus chemotaxis inhibitory protein

A secreted 14.1 kDa protein that inhibits the recruitment of neutrophils and the inflammatory response by blocking the C5a receptor and the N-formyl-methionyl-leucyl-phenylalanine receptor.

Superantigen

A bacterial protein that non-specifically activates T cells, resulting in an inappropriate and massive release of cytokines and chemokines.

Lysostaphin

A zinc metalloenzyme produced by Staphylococcus simulans that specifically lyses the S. aureus cell wall.

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Chambers, H., DeLeo, F. Waves of resistance: Staphylococcus aureus in the antibiotic era. Nat Rev Microbiol 7, 629–641 (2009). https://doi.org/10.1038/nrmicro2200

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