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Despite being a key event in the bacterial cell cycle, cell division has not been explored\n            <jats:italic>in vivo<\/jats:italic>\n            in bacterial pathogens interacting with their hosts. We discovered in\n            <jats:italic>Salmonella enterica<\/jats:italic>\n            serovar Typhimurium a gene absent in nonpathogenic bacteria and encoding a peptidoglycan synthase with 63% identity to penicillin-binding protein 3 (PBP3). PBP3 is an essential cell division-specific peptidoglycan synthase that builds the septum required to separate daughter cells. Since\n            <jats:italic>S<\/jats:italic>\n            .\u00a0Typhimurium carries genes that encode a PBP3 paralog\u2014which we named PBP3\n            <jats:sub>SAL<\/jats:sub>\n            \u2014and PBP3, we hypothesized that there are different cell division events in host and nonhost environments. To test this, we generated\n            <jats:italic>S<\/jats:italic>\n            .\u00a0Typhimurium isogenic mutants lacking PBP3\n            <jats:sub>SAL<\/jats:sub>\n            or the hitherto considered essential PBP3. While PBP3 alone promotes cell division under all conditions tested, the mutant producing only PBP3\n            <jats:sub>SAL<\/jats:sub>\n            proliferates under acidic conditions (pH \u2264 5.8) but does not divide at neutral pH. PBP3\n            <jats:sub>SAL<\/jats:sub>\n            production is tightly regulated with increased levels as bacteria grow in media acidified up to pH\u00a04.0 and in intracellular bacteria infecting eukaryotic cells. PBP3\n            <jats:sub>SAL<\/jats:sub>\n            activity is also strictly dependent on acidic pH, as shown by beta-lactam antibiotic binding assays. Live-cell imaging microscopy revealed that PBP3\n            <jats:sub>SAL<\/jats:sub>\n            alone is sufficient for\n            <jats:italic>S<\/jats:italic>\n            .\u00a0Typhimurium to divide within phagosomes of the eukaryotic cell. Additionally, we detected much larger amounts of PBP3\n            <jats:sub>SAL<\/jats:sub>\n            than those of PBP3\n            <jats:italic>in vivo<\/jats:italic>\n            in bacteria colonizing mouse target organs. Therefore, PBP3\n            <jats:sub>SAL<\/jats:sub>\n            evolved in\n            <jats:italic>S<\/jats:italic>\n            .\u00a0Typhimurium as a specialized peptidoglycan synthase promoting cell division in the acidic intraphagosomal environment.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            During bacterial cell division, daughter cells separate by a transversal structure known as the division septum. The septum is a continuum of the cell wall and therefore is composed of membrane(s) and a peptidoglycan layer. To date, actively growing bacteria were reported to have only a \u201ccell division-specific\u201d peptidoglycan synthase required for the last steps of septum formation and consequently, essential for bacterial life. Here, we discovered that\n            <jats:italic>Salmonella enterica<\/jats:italic>\n            has two peptidoglycan synthases capable of synthesizing the division septum. One of these enzymes, PBP3\n            <jats:sub>SAL<\/jats:sub>\n            , is present only in bacterial pathogens and evolved in\n            <jats:italic>Salmonella<\/jats:italic>\n            to function exclusively in acidic environments. PBP3\n            <jats:sub>SAL<\/jats:sub>\n            is used preferentially by\n            <jats:italic>Salmonella<\/jats:italic>\n            to promote cell division\n            <jats:italic>in vivo<\/jats:italic>\n            in mouse target organs and inside acidified phagosomes. Our data challenge the concept of only one essential cell division-specific peptidoglycan synthase and demonstrate that pathogens can divide in defined host locations using alternative mechanisms.\n          <\/jats:p>","DOI":"10.1128\/mbio.01685-17","type":"journal-article","created":{"date-parts":[[2018,1,5]],"date-time":"2018-01-05T13:51:59Z","timestamp":1515160319000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":45,"title":["A Specialized Peptidoglycan Synthase Promotes\n            <i>Salmonella<\/i>\n            Cell Division inside Host Cells"],"prefix":"10.1128","volume":"8","author":[{"given":"S\u00f3nia","family":"Castanheira","sequence":"first","affiliation":[{"name":"Laboratorio de Pat\u00f3genos Bacterianos Intracelulares, Centro Nacional de Biotecnolog\u00eda, Consejo Superior de Investigaciones Cient\u00edficas (CNB-CSIC), Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan J.","family":"Cestero","sequence":"additional","affiliation":[{"name":"Laboratorio de Pat\u00f3genos Bacterianos Intracelulares, Centro Nacional de Biotecnolog\u00eda, Consejo Superior de Investigaciones Cient\u00edficas (CNB-CSIC), Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gadea","family":"Rico-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Laboratorio de Pat\u00f3genos Bacterianos Intracelulares, Centro Nacional de Biotecnolog\u00eda, Consejo Superior de Investigaciones Cient\u00edficas (CNB-CSIC), Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Garc\u00eda","sequence":"additional","affiliation":[{"name":"Laboratorio de Pat\u00f3genos Bacterianos Intracelulares, Centro Nacional de Biotecnolog\u00eda, Consejo Superior de Investigaciones Cient\u00edficas (CNB-CSIC), Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe","family":"Cava","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Infection Medicine Sweden, Department of Molecular Biology, Ume\u00e5 University, Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan A.","family":"Ayala","sequence":"additional","affiliation":[{"name":"Centro de Biolog\u00eda Molecular Severo Ochoa, Consejo Superior de Investigaciones Cient\u00edficas (CBMSO-CSIC), Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4268-2316","authenticated-orcid":false,"given":"M. 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