{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T11:58:58Z","timestamp":1791028738434,"version":"4.1.0"},"reference-count":0,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[1999,10,1]],"date-time":"1999-10-01T00:00:00Z","timestamp":938736000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microbial Drug Resistance"],"published-print":{"date-parts":[[1999,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Tn\n                    <jats:italic toggle=\"yes\">551<\/jats:italic>\n                    inactivation has identified several determinants\u2014\n                    <jats:italic toggle=\"yes\">fem<\/jats:italic>\n                    or auxiliary genes\u2014that, in addition to the\n                    <jats:italic toggle=\"yes\">mecA<\/jats:italic>\n                    gene, are also critical for the expression of high-level and homogeneous resistance to methicillin. Genetic and\/or biochemical analysis has shown that of the nearly dozen aux mutations described so far most are in genes involved in cell wall synthesis (\n                    <jats:italic toggle=\"yes\">murE, pbp2, glmM, glnR, femA\/B, Um, etc.<\/jats:italic>\n                    ) or in complex regulatory functions (\n                    <jats:italic toggle=\"yes\">sigmaB<\/jats:italic>\n                    ), suggesting that optimal expression of resistance may involve the cooperative functioning of a number of genes in cell wall metabolism as well as stress response. The exact mechanism of these functions is not known. In an attempt to explore this unusual aspect of methicillin resistance more fully, a Tn\n                    <jats:italic toggle=\"yes\">551<\/jats:italic>\n                    transposon library, constructed in the background of the highly and homogeneously methicillin-resistant\n                    <jats:italic toggle=\"yes\">Staphylococcus aureus<\/jats:italic>\n                    strain COL, was screened for all independent insertional mutants in which the level of methicillin resistance of the parental strain (MIC, 1,600 \u03bcg\/ml) was reduced by at least 15-fold and up to 500-fold. We now describe the sequencing of 21 Tn\n                    <jats:italic toggle=\"yes\">551<\/jats:italic>\n                    -inactivated genes and their vicinities in 23 new auxiliary mutants that have been studied before. Using the inverted polymerase chain reaction (IPCR), we amplified fragments corresponding to the right and left junction of the Tn\n                    <jats:italic toggle=\"yes\">551<\/jats:italic>\n                    insertions, which were then sequenced by primer walking. The two largest groups of these new auxiliary genes encoded either proteins of unknown functions (6 genes) or showed homology with genes encoding proteins involved with putative sensory\/regulatory activities (7 genes: protein kinases, ABC transporters, and a catabolite control protein). Sequencing upstream and down-stream allowed the identification of a number of additional open reading frames, some of which may also include functions relevant for the expression of antibiotic resistance.\n                  <\/jats:p>","DOI":"10.1089\/mdr.1999.5.163","type":"journal-article","created":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T12:41:03Z","timestamp":1233232863000},"page":"163-175","source":"Crossref","is-referenced-by-count":139,"title":["Antibiotic Resistance As a Stress Response: Complete Sequencing of a Large Number of Chromosomal Loci in\n                    <i>Staphylococcus aureus<\/i>\n                    Strain COL That Impact on the Expression of Resistance to Methicillin"],"prefix":"10.1177","volume":"5","author":[{"given":"H.","family":"De Lencastre","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.W.","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.G.","family":"Pinho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.M.","family":"Ludovice","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Filipe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Gardete","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Sobral","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Gill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Chung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Tomasz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[1999,10]]},"container-title":["Microbial Drug Resistance"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/mdr.1999.5.163","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/mdr.1999.5.163","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T18:13:38Z","timestamp":1770747218000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/full\/10.1089\/mdr.1999.5.163"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,10]]},"references-count":0,"journal-issue":{"issue":"3","published-print":{"date-parts":[[1999,10]]}},"alternative-id":["10.1089\/mdr.1999.5.163"],"URL":"https:\/\/doi.org\/10.1089\/mdr.1999.5.163","relation":{},"ISSN":["1076-6294","1931-8448"],"issn-type":[{"value":"1076-6294","type":"print"},{"value":"1931-8448","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999,10]]}}}