{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T12:02:08Z","timestamp":1778673728049,"version":"3.51.4"},"reference-count":34,"publisher":"Proceedings of the National Academy of Sciences","issue":"3","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2002,2,5]]},"abstract":"<jats:p>\n            Inactivation of the recently identified\n            <jats:italic>murMN<\/jats:italic>\n            operon in penicillin-resistant strains of\n            <jats:italic>Streptococcus pneumoniae<\/jats:italic>\n            was shown already to cause two major effects: elimination of branched-structured muropeptides from the cell wall and complete loss of penicillin resistance. We now show that cells with inactivated\n            <jats:italic>murMN<\/jats:italic>\n            also have a third phenotype: an increased susceptibility to lysis when exposed to low concentrations of fosfomycin,\n            <jats:sc>d<\/jats:sc>\n            -cycloserine, vancomycin, and nisin, indicating a wide-spectrum hypersensitivity to inhibitors of both early and late stages of cell wall biosynthesis. Mutants of\n            <jats:italic>murMN<\/jats:italic>\n            also lysed faster than the parental strain when treated with the detergent deoxycholate. Several different alleles of\n            <jats:italic>murM<\/jats:italic>\n            cloned in plasmid pLS578 and introduced into a\n            <jats:italic>murM<\/jats:italic>\n            deletion mutant of the penicillin-resistant strain Pen6 were able to reconstitute each one of the three mutant phenotypes: the highly branched cell wall structure, original high level of penicillin resistance, and normal sensitivity to lysis. In a penicillin-susceptible strain the same experiments caused increased concentration of cell wall branched peptides and suppression of sensitivity to antibiotic induced lysis. The observations suggest that the\n            <jats:italic>murMN<\/jats:italic>\n            operon plays a key role in the regulation of a stress-response pathway that can be triggered by perturbation of cell wall biosynthesis in\n            <jats:italic>S. pneumoniae<\/jats:italic>\n            .\n          <\/jats:p>","DOI":"10.1073\/pnas.032671699","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T14:36:44Z","timestamp":1027694204000},"page":"1550-1555","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":61,"title":["The\n            <i>murMN<\/i>\n            operon: A functional link between antibiotic resistance and antibiotic tolerance in\n            <i>Streptococcus<\/i>\n            <i>pneumoniae<\/i>"],"prefix":"10.1073","volume":"99","author":[{"given":"Sergio R.","family":"Filipe","sequence":"first","affiliation":[{"name":"Laboratory of Microbiology, The Rockefeller University, New York, NY 10021; and Molecular Genetics Unit, Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica, Universidade Nova de Lisboa, 2780 Oeiras, Portugal"}]},{"given":"Elena","family":"Severina","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology, The Rockefeller University, New York, NY 10021; and Molecular Genetics Unit, Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica, Universidade Nova de Lisboa, 2780 Oeiras, Portugal"}]},{"given":"Alexander","family":"Tomasz","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology, The Rockefeller University, New York, NY 10021; and Molecular Genetics Unit, Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica, Universidade Nova de Lisboa, 2780 Oeiras, Portugal"}]}],"member":"341","published-online":{"date-parts":[[2002,2,5]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.14.5415"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.080067697"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.182.23.6798-6805.2000"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M004675200"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M106425200"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.79.2.137"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.17.3.434"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1089\/mdr.1998.4.325"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(88)90489-1"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2000.01777.x"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.170.5.2143-2147.1988"},{"key":"e_1_3_3_12_2","volume-title":"Current Protocols in Molecular Biology","author":"Ausubel F M","year":"1996","unstructured":"F M Ausubel, R Brent, R E Kingston, D D Moore, J G Seidman, J A Smith, K Struhl Current Protocols in Molecular Biology (Wiley, New York, 1996)."},{"key":"e_1_3_3_13_2","volume-title":"Molecular Cloning: A Laboratory Manual","author":"Sambrook J","year":"1989","unstructured":"J Sambrook, E F Fritsch, T Maniatis Molecular Cloning: A Laboratory Manual (Cold Spring Harbor Lab. 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