{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T17:50:31Z","timestamp":1775152231180,"version":"3.50.1"},"reference-count":62,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Microbiol"],"published-print":{"date-parts":[[2011,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>The \u03b2-lactamase (<jats:italic>bla<\/jats:italic>) locus, which confers resistance to penicillins only, may control the transcription of <jats:italic>mecA<\/jats:italic>, the central element of methicillin resistance, which is embedded in a polymorphic heterelogous chromosomal cassette (the SCC<jats:italic>mec<\/jats:italic> element). In order to assess the eventual correlation between <jats:italic>bla<\/jats:italic> allotypes and genetic lineages, SCC<jats:italic>mec<\/jats:italic> types and\/or \u03b2-lactam resistance phenotypes, the allelic variation on the <jats:italic>bla<\/jats:italic> locus was evaluated in a representative collection of 54 international epidemic methicillin-resistant <jats:italic>Staphylococcus aureus<\/jats:italic> (MRSA) clinical strains and, for comparative purposes, also in 24 diverse methicillin-susceptible <jats:italic>S. aureus<\/jats:italic> (MSSA) strains.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Internal fragments of <jats:italic>blaZ<\/jats:italic> (the \u03b2-lactamase structural gene) were sequenced for all strains. A subset of strains, representative of <jats:italic>blaZ<\/jats:italic> allotypes, was further characterized by sequencing of internal fragments of the <jats:italic>blaZ<\/jats:italic> transcriptional regulators, <jats:italic>blaI<\/jats:italic> and <jats:italic>blaR1<\/jats:italic>. Thirteen allotypes for <jats:italic>blaZ<\/jats:italic>, nine for <jats:italic>blaI<\/jats:italic> and 12 for <jats:italic>blaR1<\/jats:italic> were found. In a total of 121 unique single-nucleotide polymorphisms (SNP) detected, no frameshift mutations were identified and only one nonsense mutation within <jats:italic>blaZ<\/jats:italic> was found in a MRSA strain. On average, <jats:italic>blaZ<\/jats:italic> alleles were more polymorphic among MSSA than in MRSA (14.7 <jats:italic>vs<\/jats:italic> 11.4 SNP\/allele). Overall, <jats:italic>blaR1<\/jats:italic> was the most polymorphic gene with an average of 24.8 SNP\/allele. No correlation could be established between <jats:italic>bla<\/jats:italic> allotypes and genetic lineages, SCC<jats:italic>mec<\/jats:italic> types and\/or \u03b2-lactam resistance phenotypes. In order to estimate the selection pressure acting on the <jats:italic>bla<\/jats:italic> locus, the average dN\/dS values were computed. In the three genes and in both collections dN\/dS ratios were significantly below 1.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>The data strongly suggests the existence of a purifying selection to maintain the <jats:italic>bla<\/jats:italic> locus fully functional even on MRSA strains. Although, this is in agreement with the notion that in most clinical MRSA strains <jats:italic>mecA<\/jats:italic> gene is under the control of the <jats:italic>bla<\/jats:italic> regulatory genes, these findings also suggest that the apparently redundant function of <jats:italic>blaZ<\/jats:italic> gene for the MRSA resistant phenotype is still important for these strains. In addition, the data shows that the sensor-inducer <jats:italic>blaR1<\/jats:italic> is the primary target for the accumulation of mutations in the <jats:italic>bla<\/jats:italic> locus, presumably to modulate the response to the presence of \u03b2-lactam antibiotic.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2180-11-76","type":"journal-article","created":{"date-parts":[[2011,4,20]],"date-time":"2011-04-20T18:19:31Z","timestamp":1303323571000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Evidence for a purifying selection acting on the \u03b2-lactamase locus in epidemic clones of methicillin-resistant Staphylococcus aureus"],"prefix":"10.1186","volume":"11","author":[{"given":"Catarina","family":"Milheiri\u00e7o","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Portelinha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ludwig","family":"Krippahl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Herm\u00ednia","family":"de Lencastre","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Duarte C","family":"Oliveira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2011,4,15]]},"reference":[{"issue":"15","key":"1371_CR1","doi-asserted-by":"publisher","first-page":"1763","DOI":"10.1001\/jama.298.15.1763","volume":"298","author":"RM Klevens","year":"2007","unstructured":"Klevens RM, Morrison MA, Nadle J, Petit S, Gershman K, Ray S, Harrison LH, Lynfield R, Dumyati G, Townes JM, et al: Invasive methicillin-resistant Staphylococcus aureus infections in the United States. 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