1 Gram-positive Bacteria Typing and Research Unit, Molecular Genetics Research Unit, School of Biomedical Sciences, Curtin University of Technology, GPO Box U1987, Perth, WA 6845; 2 Department of Microbiology and Infectious Diseases, Royal Perth Hospital, Perth, Western Australia, Australia
Received 22 May 2002; returned 4 July 2002; revised 3 September 2002; accepted 10 September 2002
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Abstract |
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Introduction |
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The mecA gene codes for resistance to methicillin and all other ß-lactam antibiotics in S. aureus.2 mecA is also found in other species of staphylococci and is highly conserved except for a silent, single-base mutation in some strains that creates an XbaI site.8 The mecA gene is regulated by two genes, mecR1 and mecI, located upstream of the mecA gene,9 and this region, together with mecA, has been referred to as the mec complex.10 The mecR1 gene encodes a transmembrane inducer of mecA consisting of membrane-spanning (MS) and penicillin-binding (PB) domains.9 The mecI gene encodes a strong repressor of mecA9 and consequently strains such as N315 with intact mecR1 and mecI can appear methicillin sensitive in susceptibility tests.9 The mecR1 and mecI genes have a high degree of homology to the blaR1 and blaI genes, which regulate ß-lactamase production,9 and studies have shown that the blaR1blaI complex is able to regulate the expression of the mecA gene.11 MRSA strains that have a dysfunctional regulatory region can either express mecA constitutively, or they can use the ß-lactamase regulatory genes to optimally express mecA because BlaR1 is a strong inducer of mecA and BlaI is a weak repressor.9,11
Studies on the mecR1mecI region have shown that there is considerable genomic diversity in the mec complex.10,12 Currently, five different classes of the mec complex have been described. The Class A complex has intact mecR1 and mecI genes. In the Class B complex the PB domain of mecR1 and the complete mecI gene are truncated by a partial copy of IS1272. The Class C complex has two variants, C1 and C2. In the Class C1 complex, the PB domain of mecR1 and the whole of mecI are truncated by IS431, whereas in the Class C2 complex, both the MS and PB domains of mecR1 as well as mecI are truncated by IS431. In Class D mec complex mecI is deleted and the PB domain of mecR1 is truncated.10 The mec complex is part of a larger region known as the staphylococcal cassette chromosome mec (SCCmec).13 Four types of SCCmec have been described.13,14 The types are different because SCCmec can acquire different genetic elements. Consequently, different SCCmec regions can have the same mec complex. Therefore analysis of the mec complex is more likely to reflect the ancestral origin of mecA because SCCmec can acquire and/or lose_elements, whereas the mec complexes are less likely to undergo additional deletions and_mutations once mecA is being expressed. The mec complex would therefore appear to be a useful tool to compare the ancestry of MRSA when combined with other molecular methods.
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Materials and methods |
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Results and discussion |
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Nine of the English EMRSA studied carried the Class B mec complex but only six were found in the CHEF B cluster. The other three English EMRSA were only distantly related to the CHEF B cluster isolates. This is especially so for EMRSA-15, which is only 40% related to the CHEF B cluster isolates. The two most likely explanations of these results are that a strain has acquired the mec complex and then some have evolved to give widely different CHEF patterns, or alternatively, strains with different genetic backgrounds have acquired similar mec complexes. Recent studies using MLST and DNA microarray techniques have indicated that the latter hypothesis may better explain this phenomenon.5,6
The Class A and Class B mec complexes were found in both classic MRSA and later MRSA isolates. Although some of the later isolates were genetically related to the classic isolates and had the same class of mec complex, some of them were not related to each other. In a recent study, an Iberian MRSA was found to be a descendant of an early methicillin-susceptible S. aureus.4 In another study, evidence has been presented for at least five horizontal transfers of mecA into genetically distinct S. aureus.6 Both studies have demonstrated the co-existence of descendants of old clones and new clones created by horizontal transfer of the methicillin resistance gene.
The analysis of the mec complex together with the CHEF patterns of these epidemic strains may support the global spread of epidemic clones and their possible ancestry. However, more comprehensive methods such as using MLST or DNA microarray techniques may give a more definite conclusion.
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Acknowledgements |
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Footnotes |
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References |
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