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PG precursors are translocated across the cytoplasmic membrane by the lipid carrier undecaprenyl phosphate (Und\u2010P) where they are incorporated into the PG superstructure. Previously, we found that one of our <jats:italic>Escherichia coli<\/jats:italic> laboratory strains (CS109) harbors a missense mutation in <jats:italic>uppS<\/jats:italic>, which encodes an enzymatically defective Und\u2010P(P) synthase. Here, we show that CS109 cells lacking the bifunctional aPBP PBP1B (penicillin binding protein 1B) lyse during exponential growth at elevated temperature. PBP1B lysis was reversed by: (i) reintroducing wild\u2010type <jats:italic>uppS<\/jats:italic>, (ii) increasing the availability of PG precursors or (iii) overproducing PBP1A, a related bifunctional PG synthase. In addition, inhibiting the catalytic activity of PBP2 or PBP3, two monofunctional bPBPs, caused CS109 cells to lyse. Limiting the precursors required for Und\u2010P synthesis in MG1655, which harbors a wild\u2010type allele of <jats:italic>uppS<\/jats:italic>, also promoted lysis in mutants lacking PBP1B or bPBP activity. Thus, simultaneous inhibition of Und\u2010P production and PG synthases provokes a synergistic response that leads to cell lysis. These findings suggest a biological connection that could be exploited in combination therapies.<\/jats:p>","DOI":"10.1111\/mmi.14265","type":"journal-article","created":{"date-parts":[[2019,4,25]],"date-time":"2019-04-25T16:12:56Z","timestamp":1556208776000},"page":"233-248","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Simultaneously inhibiting undecaprenyl phosphate production and peptidoglycan synthases promotes rapid lysis in <i>Escherichia coli<\/i>"],"prefix":"10.1111","volume":"112","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1351-7730","authenticated-orcid":false,"given":"Matthew A.","family":"Jorgenson","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology University of Arkansas for Medical Sciences Little Rock AR 72205 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William J.","family":"MacCain","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology University of Arkansas for Medical Sciences Little Rock AR 72205 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernadette M.","family":"Meberg","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences University of North Dakota School of Medicine and Health Sciences Grand Forks ND 58202 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suresh","family":"Kannan","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology University of Arkansas for Medical Sciences Little Rock AR 72205 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph C.","family":"Bryant","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology University of Arkansas for Medical Sciences Little Rock AR 72205 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin D.","family":"Young","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology University of Arkansas for Medical Sciences Little Rock AR 72205 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,5,6]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1128\/jb.179.13.4277-4284.1997"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.04.033"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/la991013x"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1099390"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2012.08103.x"},{"key":"e_1_2_6_7_1","doi-asserted-by":"crossref","first-page":"7142","DOI":"10.1016\/S0021-9258(18)48216-6","article-title":"Biosynthesis of enterobacterial common antigen in Escherichia coli. 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