{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T05:33:20Z","timestamp":1768714400038,"version":"3.49.0"},"reference-count":44,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,2,16]],"date-time":"2022-02-16T00:00:00Z","timestamp":1644969600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FEDER funds through COMPETE2020","award":["LISBOA-01-0145-FEDER-007660"],"award-info":[{"award-number":["LISBOA-01-0145-FEDER-007660"]}]},{"name":"FEEI \u2013 \u201cFundos Estruturais e de Investimento\u201d from \u201cPrograma Operacional Regional Lisboa 2020\u201d and by national funds from FCT \u2013 \u201cFunda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia\u201d, Portugal.","award":["LISBOA-01-0145-FEDER-016417"],"award-info":[{"award-number":["LISBOA-01-0145-FEDER-016417"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>The acquisition of the resistance determinant mecA by Staphylococcus aureus is of major clinical importance, since it confers a resistant phenotype to virtually the entire large family of structurally diverse \u03b2-lactam antibiotics. While the common resistance determinant mecA is essential, the optimal expression of the resistance phenotype also requires additional factors. Previous studies showed that the great majority of clinical isolates of methicillin-resistant S. aureus (MRSA) have a heterogeneous resistant phenotype, and we observed that strains carrying methicillin genetic determinants other than mecA also produce similar heterogeneous phenotypes. All these strains were able to express high and homogeneous levels of oxacillin resistance when sub-inhibitory concentrations of mupirocin, an effector of the stringent stress response, were added to growth media. Our studies show that the gene gmk, involved in guanine metabolism, was one of the first genes to exhibit mutations in homoresistant (H*R) derivatives obtained through serial passages (with increasing concentrations of oxacillin) of the prototype mecC-carrying MRSA strain LGA251. All these observations led us to propose that a common molecular mechanism for the establishment of high and homogeneous oxacillin resistance must be present among isolates carrying different methicillin resistance determinants. In this work, we tested this hypothesis using whole-genome sequencing (WGS) to compare isogenic populations differing only in their degrees of oxacillin resistance and carrying various methicillin genetic determinants<\/jats:p>","DOI":"10.3390\/antibiotics11020255","type":"journal-article","created":{"date-parts":[[2022,2,16]],"date-time":"2022-02-16T20:26:41Z","timestamp":1645043201000},"page":"255","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Impact of the Stringent Stress Response on the Expression of Methicillin Resistance in Staphylococcaceae Strains Carrying mecA, mecA1 and mecC"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2825-8850","authenticated-orcid":false,"given":"Catarina","family":"Milheiri\u00e7o","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Genetics, Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica Ant\u00f3nio Xavier (ITQB NOVA), Universidade Nova de Lisboa, 2780-157 Oeiras, Portugal"}]},{"given":"Alexander","family":"Tomasz","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology & Infectious Diseases, The Rockefeller University, New York, NY 10065, USA"}]},{"given":"Herm\u00ednia","family":"de Lencastre","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics, Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica Ant\u00f3nio Xavier (ITQB NOVA), Universidade Nova de Lisboa, 2780-157 Oeiras, Portugal"},{"name":"Laboratory of Microbiology & Infectious Diseases, The Rockefeller University, New York, NY 10065, USA"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,16]]},"reference":[{"key":"ref_1","first-page":"2112","article-title":"Methicillin-susceptible and Methicillin-resistant Staphylococcus aureus Bacteremia: Nationwide Estimates of 30-Day Readmission, In-hospital Mortality, Length of Stay, and Cost in the United States","volume":"69","author":"Inagaki","year":"2019","journal-title":"Clin. 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