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The Staphylococcus aureus “superbug”
Timothy J. Foster
Microbiology Department, Moyne Institute of Preventive Medicine, Trinity College, Dublin, Ireland.
Address correspondence to: Timothy J. Foster, Microbiology Department, Moyne Institute of Preventive Medicine, Trinity College, Dublin 2, Ireland. Phone: 353-1-6082014; Fax: 353-1-6799294; E-mail: tfoster@tcd.ie.
Find articles by Foster, T. in: JCI | PubMed | Google Scholar
Published December 15, 2004 - More info
J Clin Invest. 2004;114(12):1693–1696. https://doi.org/10.1172/JCI23825.
© 2004 The American Society for Clinical Investigation
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Methicillin-resistant S. aureus
Healthy individuals have a small but finite risk of contracting an invasive infection caused by S. aureus, and this risk is increased among carriers. Hospital patients who are catheterized or who have been treated surgically have a significantly higher rate of infection. In some, but not all, developed countries, many nosocomial infections are caused by S. aureus strains that are multiply resistant to antibiotics — known as methicillin-resistant Staphylococcus aureus (MRSA) (3, 4) — although the acronym MRSA is somewhat misleading because the semisynthetic β-lactam methicillin is no longer used to treat S. aureus infections. In MRSA, the horizontally acquired mecA gene encodes a penicillin-binding protein, PBP2a, which is intrinsically insensitive to methicillin and all β-lactams that have been developed, including the isoxazoyl penicillins (e.g., oxacillin) that superceded methicillin, in addition to the broad spectrum β-lactams (third-generation cephalosporins, cefamycins, and carbapenems) that were introduced primarily to treat infections caused by Gram-negative bacteria (4) (Figure 1). In contrast to nosocomial MRSA strains, which are usually multidrug resistant, the recently emerged community-acquired MRSA (CA-MRSA) strains are susceptible to drugs other than β-lactams (5).
Figure 1Schematic diagram illustrating how S. aureus acquires resistance to methicillin and its ability to express different virulence factors. The bacterium expresses surface protein adhesins and WTA and also secretes many toxins and enzymes by activation of chromosomal genes. Adhesins and WTA have been implicated in nasal and skin colonization. Resistance to methicillin is acquired by insertion of a horizontally transferred DNA element called SCCmec. Five different SCCmec elements can integrate at the same site in the chromosome by a Campbell-type mechanism involving site-specific recombination. The mecA gene encodes a novel β-lactam–insensitive penicillin binding protein, PBP2a, which continues to synthesize new cell wall peptidoglycan even when the normal penicillin binding proteins are inhibited. Some virulence factors such as PVL and the chemotaxis inhibitory protein, CHIP, are encoded by genes located on lysogenic bacteriophages.
The term MRSA is synonymous with multidrug-resistant S. aureus because many nosocomial MRSA strains are resistant to most commonly used antibiotics. The glycopeptide vancomycin was the last available drug to which this organism had remained uniformly sensitive until recent reports of low-level glycopeptide resistance (6) and, very recently, the transfer of high-level vancomycin resistance from Enterococcus to S. aureus (7). Although new drugs, including linezolid and synercid, have recently been introduced to treat MRSA infections (8), there is a worrying lack of novel drugs in the pipeline.
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The S. aureus population is clonal
The study by Melles et al. reported in this issue of the JCI (17) examines the major questions about natural populations of S. aureus concerning clonality and virulence. The authors examined 829 S. aureus strains from healthy donors from the city of Rotterdam in The Netherlands. Selective amplified fragment length polymorphism (AFLP) amplification analysis was used to compare genetic relatedness of strains, and this analysis revealed the existence of 3 major and 2 minor genetic clusters, subsequently confirmed by multilocus sequence typing (MLST) (Figure 2). The authors therefore concluded that the S. aureus population is clonal. These clusters corresponded to the predominant groups identified in a recent study of carriage isolates from the county of Oxfordshire in the United Kingdom using MLST (18). Thus the same clonal lineages appear to be dominant in 2 distinct geographic locations.
Figure 2Principal component analysis of 1,056 S. aureus strains reveals genetic clusters of hypervirulent clones (17). The different cubes, plotted here in a 3D space and colored according to their source, represent each S. aureus strain analyzed in the Melles et al. study. The 5 circles indicate the 3 major (I, II, and III) and 2 minor (IVa and IVb) different phylogenetic clusters identified by AFLP. While strains from each of the genetic clusters are essentially able to cause invasive disease, some clusters contain proportionally more invasive isolates.
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