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The <jats:italic>N. gonorrhoeae<\/jats:italic> cell wall is critical for maintaining envelope integrity, resisting immune cell killing and production of cytotoxic peptidoglycan (PG) fragments. Deletion of the <jats:italic>N. gonorrhoeae<\/jats:italic> strain FA1090 genes encoding two predicted low\u2010molecular\u2010mass, penicillin\u2010binding proteins (LMM PBPs), DacB and DacC, substantially altered the PG cross\u2010linking. Loss of the DacB peptidase resulted in global alterations to the PG composition, while loss of the DacC protein affected a much narrower subset of PG peptide components. A double \u0394<jats:italic>dacB\/<\/jats:italic>\u0394<jats:italic>dacC<\/jats:italic> mutant resembled the \u0394<jats:italic>dacB<\/jats:italic> single mutant, but had an even greater level of cross\u2010linked PG. While single \u0394<jats:italic>dacB<\/jats:italic> or \u0394<jats:italic>dacC<\/jats:italic> mutants did not show any major phenotypes, the \u0394<jats:italic>dacB\/<\/jats:italic>\u0394<jats:italic>dacC<\/jats:italic> mutant displayed an altered cellular morphology, decreased resistance to antibiotics and increased sensitivity to detergent\u2010mediated death. Loss of the two proteins also drastically reduced the number of Type IV pili (Tfp), a critical virulence factor. The decreased piliation reduced transformation efficiency and correlated with increased growth rate. While these two LMM PBPs differentially alter the PG composition, their overlapping effects are essential to proper envelope function and expression of factors critical for pathogenesis.<\/jats:p>","DOI":"10.1111\/mmi.13955","type":"journal-article","created":{"date-parts":[[2018,3,24]],"date-time":"2018-03-24T23:38:53Z","timestamp":1521934733000},"page":"135-149","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["The low\u2010molecular\u2010mass, penicillin\u2010binding proteins DacB and DacC combine to modify peptidoglycan cross\u2010linking and allow stable Type IV pilus expression in <i>Neisseria gonorrhoeae<\/i>"],"prefix":"10.1111","volume":"109","author":[{"given":"Kyle P.","family":"Obergfell","sequence":"first","affiliation":[{"name":"Department of Microbiology\u2010Immunology Northwestern University's Feinberg School of Medicine Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5300-2403","authenticated-orcid":false,"given":"Ryan E.","family":"Schaub","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology University of Wisconsin\u2010Madison Madison WI 53706 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren L.","family":"Priniski","sequence":"additional","affiliation":[{"name":"Department of Microbiology\u2010Immunology Northwestern University's Feinberg School of Medicine Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph P.","family":"Dillard","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology University of Wisconsin\u2010Madison Madison WI 53706 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8651-0375","authenticated-orcid":false,"given":"H Steven","family":"Seifert","sequence":"additional","affiliation":[{"name":"Department of Microbiology\u2010Immunology Northwestern University's Feinberg School of Medicine Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,4,15]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(05)80360-2"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.46.12.3744-3749.2002"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M304749200"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.19.2.316"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/femsre\/fuu001"},{"key":"e_1_2_6_7_1","first-page":"144","volume-title":"Mathematics and Natural Sciences","author":"Bottcher J.P.","year":"2011"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02103-16"},{"key":"e_1_2_6_9_1","volume-title":"Antibiotic Resistance Threats in the United States, 2013","author":"Centers for Disease Control Prevention","year":"2013"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad2001"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.186.3.730-739.2004"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja903773f"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00506-08"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aam6512"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro885"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2011.01607.x"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.9.5697-5705.2005"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1128\/jb.163.1.69-74.1985"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1989.tb00101.x"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1128\/iai.64.2.644-652.1996"},{"key":"e_1_2_6_21_1","unstructured":"Francis Ndowa M.L.\u2010N.(2012)Global action plan to control the spread and impact of antimicrobial resistance inNeisseria gonorrhoeae. 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