Molecular epidemiology of methicillin-resistant Staphylococcus aureus

1. Introduction
Since its discovery in the 1880s, Staphylococcus aureus has been known as a potential pathogenic Grampositive bacterium. It can cause a broad variety of diseases, ranging from minor infections of the skin to
post-operative wound infections. Until the introduction of penicillin in the early 1940s and the treatment
of S. aureus infections with this antibiotic, the mortality rate of patients with a S. aureus infection was
about 80%. However, shortly after the introduction of penicillin for medical use, the first penicillinresistant strains were isolated in 1942, first in hospitals, and later on in the community. Since 1960,
around 80% of all S. aureus strains are penicillin resistant. In 1962, two years after the introduction of
methicillin, S. aureus developed resistance to methicillin through the acquisition of the mecA gene [1, 2].
2. Resistance determinant SCCmec
The resistance of S. aureus to methicillin and other ß-lactam antibiotics is caused by the mecA gene,
which encodes the 78-kDa penicillin-binding protein (PBP) 2a (or PBP2’) [3]. The 2.1-kb mecA gene is
located on a mobile genetic element, the Staphylococcal Cassette Chromosome mec (SCCmec) [4].
Currently, six main types of SCCmec (type I to VI) are distinguished, ranging in size from 20.9 to 66.9
kb (Fig. 1).
SCCmec types I (34.3 kb), IV (20.9 to 24.3 kb), V (28 kb) and VI (20.9 Kb) encode for resistance to βlactam antibiotics only. SCCmec types II (53.0 kb) and III (66.9 kb) determine multi resistance, as these

elements harbour additional drug resistance genes, which are carried on integrated plasmids, i.e.
pUB110, pI258 and pT181, and a transposon (Tn554). Plasmid pUB110 carries the ant(4′)

gene, encoding for resistance to kanamycin, tobramycin and bleomycin, and pI258 codes for resistance
to penicillins and heavy metals, such as mercury. Plasmid pT181 codes for tetracycline resistance, while
transposon Tn554 carries the ermA gene, which is responsible for inducible macrolide, lincosamide and
streptogramin (MLS) resistance (Fig. 1) [4, 9, 12]. S. aureus can also carry resistance genes on plasmids
and on other sites of the chromosome. Recently, it has been shown that SCCmec type III is a composite
element, consisting of SCCmec type III and SCCmercury, harbouring ccrC, pI258 and Tn554 [13].
Furthermore, SCCmec harbours insertion sequences, such as IS431, as well as genes responsible for the
regulation of mecA transcription, i.e. ∆mecRI (on SCCmec types I, IV, V and VI), or mecRI and mecI (on
SCCmec types II and III) [4-7, 9]. Both mecI and mecRI can be truncated by IS431 or IS1272, and this
results in a de-repression of mecA [14]. These genes are situated on the so-called mec complexes, of
which five major classes have been distinguished (Table 1) [4, 5, 14].

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