{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T01:00:14Z","timestamp":1787792414518,"version":"build-2784847793"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2022,12,13]],"date-time":"2022-12-13T00:00:00Z","timestamp":1670889600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004837","name":"Spanish Ministry of Science and Innovation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Next Generation European Union EU\/PRTR Program,","award":["PID2020-114546RB"],"award-info":[{"award-number":["PID2020-114546RB"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Following the invasion of eukaryotic cells, Salmonella enterica serovar Typhimurium replaces PBP2\/PBP3, main targets of \u03b2-lactam antibiotics, with PBP2SAL\/PBP3SAL, two homologue peptidoglycan synthases absent in Escherichia coli. PBP3SAL promotes pathogen cell division in acidic environments independently of PBP3 and shows low affinity for \u03b2-lactams that bind to PBP3 such as aztreonam, cefepime, cefotaxime, ceftazidime, ceftriaxone, cefuroxime and cefalotin.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To find compounds with high affinity for PBP3SAL to control Salmonella intracellular infections.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>An S. Typhimurium \u0394PBP3 mutant that divides using PBP3SAL and its parental wild-type strain, were exposed to a library of 1520 approved drugs in acidified (pH 4.6) nutrient-rich LB medium. Changes in optical density associated with cell filamentation, a read-out of blockage in cell division, were monitored. Compounds causing filamentation in the \u0394PBP3 mutant but not in wild-type strain\u2014the latter strain expressing both PBP3 and PBP3SAL in LB pH 4.6\u2014were selected for further study. The bactericidal effect due to PBP3SAL inhibition was evaluated in vitro using a bacterial infection model of cultured fibroblasts.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The cephalosporin cefotiam exhibited higher affinity for PBP3SAL than for PBP3 in bacteria growing in acidified LB pH 4.6 medium. Cefotiam also proved to be effective against intracellular Salmonella in a PBP3SAL-dependent manner. Conversely, cefuroxime, which has higher affinity for PBP3, showed decreased effectiveness in killing intracellular Salmonella.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Antibiotics with affinity for PBP3SAL, like the cephalosporin cefotiam, have therapeutic value for treating Salmonella intracellular infections.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkac422","type":"journal-article","created":{"date-parts":[[2022,12,13]],"date-time":"2022-12-13T18:27:46Z","timestamp":1670956066000},"page":"512-520","source":"Crossref","is-referenced-by-count":5,"title":["Affinity of cefotiam for the alternative penicillin binding protein PBP3SAL used by <i>Salmonella<\/i> inside host eukaryotic cells"],"prefix":"10.1093","volume":"78","author":[{"given":"Juan J","family":"Cestero","sequence":"first","affiliation":[{"name":"Laboratory of Intracellular Bacterial Pathogens, National Center for Biotechnology (CNB-CSIC) , Madrid , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00f3nia","family":"Castanheira","sequence":"additional","affiliation":[{"name":"Laboratory of Intracellular Bacterial Pathogens, National Center for Biotechnology (CNB-CSIC) , Madrid , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henar","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Laboratory of Intracellular Bacterial Pathogens, National Center for Biotechnology (CNB-CSIC) , Madrid , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d3scar","family":"Zaragoza","sequence":"additional","affiliation":[{"name":"Mycology Reference Laboratory, National Center for Microbiology, Instituto de Salud Carlos III , Madrid , 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