Development of methicillin resistance in clinical isolates of Staphylococcus sciuri by transcriptional activation of the mecA homologue native to s.
The beta-lactam resistance gene mecA was acquired by Staphylococcus aureus from an extraspecies source. The search for the possible origin of this gene has led to the identification of a close structural homologue of mecA as a native gene in the animal species Staphylococcus sciuri. Surprisingly, the overwhelming majority of S. sciuri isolates were fully susceptible to beta-lactam antibiotics in spite of the ubiquitous presence of the mecA homologue in the bacteria. We now describe two unusual S. sciuri strains isolated from humans-SS-37 and SS-41-that showed resistance to methicillin associated with high rates of transcription of the mecA homologue and production of a protein resembling penicillin binding protein 2a, the gene product of S. aureus mecA. In strain SS-37 increased transcription of the mecA homologue was related to insertion of an IS256 element upstream of the structural gene, and strain SS-41 had single nucleotide alterations in the promoter region of the mecA homologue which appear to be related to up-regulation of the rate of transcription. A third methicillin-resistant human isolate of S. sciuri that carries both the native mecA homologue and a methicillin-resistant S. aureus (MRSA) type mecA, strain K3, was now shown to be unstable in the absence of drug selection, causing the segregation of antibiotic-susceptible cells accompanied by the loss of the MRSA type mecA. These observations illustrate the remarkable variety of strategies available to bacteria for acquiring mechanisms of drug resistance in the in vivo environment.
Couto
Isabel
I
Molecular Genetics Unit, Instituto de Tecnologia Química e Biológica da Universidade Nova de Lisboa, 2780-156 Oeiras, Portugal.
Wu
Shang Wei
SW
Tomasz
Alexander
A
de Lencastre
Hermínia
H
D001426:Bacterial Proteins; D001483:Base Sequence; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004251:DNA Transposable Elements; D019143:Evolution, Molecular; D006602:Hexosyltransferases; D006801:Humans; D008712:Methicillin / Q000494:pharmacology; D016106:Methicillin Resistance / Q000235:genetics*; D008969:Molecular Sequence Data; D002267:Muramoylpentapeptide Carboxypeptidase / Q000235:genetics / Q000378:metabolism*; D009693:Nucleic Acid Hybridization; D046915:Penicillin-Binding Proteins; D010406:Penicillins / Q000494:pharmacology; D010458:Peptidyl Transferases; D017422:Sequence Analysis, DNA; D012689:Sequence Homology, Nucleic Acid; D013210:Staphylococcus / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D001426:Bacterial Proteins; D002352:Carrier Proteins; D004251:DNA Transposable Elements; D046915:Penicillin-Binding Proteins; D010406:Penicillins; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase; D008712:Methicillin