{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T13:52:04Z","timestamp":1792072324809,"version":"4.4.0"},"reference-count":42,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2017,1,1]],"date-time":"2017-01-01T00:00:00Z","timestamp":1483228800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Fonds der chemischen Industrie"},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["HA 6830\/1-1"],"award-info":[{"award-number":["HA 6830\/1-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Bacteriol"],"published-print":{"date-parts":[[2017,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The cell division protein GpsB is a regulator of the penicillin binding protein A1 (PBP A1) in the Gram-positive human pathogen<jats:named-content content-type=\"genus-species\">Listeria monocytogenes<\/jats:named-content>. Penicillin binding proteins mediate the last two steps of peptidoglycan biosynthesis as they polymerize and cross-link peptidoglycan strands, the main components of the bacterial cell wall. It is not known what other processes are controlled by GpsB.<jats:named-content content-type=\"genus-species\">L. monocytogenes<\/jats:named-content><jats:italic>gpsB<\/jats:italic>mutants are unable to grow at 42\u00b0C, but we observed that spontaneous suppressors correcting this defect arise on agar plates with high frequency. We here describe a first set of<jats:italic>gpsB<\/jats:italic>suppressors that mapped to the<jats:italic>clpC<\/jats:italic>and<jats:italic>murZ<\/jats:italic>genes. While ClpC is the ATPase component of the Clp protease, MurZ is a paralogue of the listerial UDP\u2013<jats:italic>N<\/jats:italic>-acetylglucosamine (UDP-GlcNAc) 1-carboxyvinyltransferase MurA. Both enzymes catalyze the enolpyruvyl transfer from phosphoenolpyruvate to UDP-GlcNAc, representing the first committed step of peptidoglycan biosynthesis. We confirmed that clean deletion of the<jats:italic>clpC<\/jats:italic>or<jats:italic>murZ<\/jats:italic>gene suppressed the \u0394<jats:italic>gpsB<\/jats:italic>phenotype. It turned out that the absence of either gene leads to accumulation of MurA, and we show that artificial overexpression of MurA alone was sufficient for suppression. Inactivation of other UDP-GlcNAc-consuming pathways also suppressed the heat-sensitive growth of the \u0394<jats:italic>gpsB<\/jats:italic>mutant, suggesting that an increased influx of precursor molecules into peptidoglycan biosynthesis can compensate for the lack of GpsB. Our results support a model according to which PBP A1 becomes misregulated and thus toxic in the absence of GpsB due to unproductive consumption of cell wall precursor molecules.<\/jats:p><jats:p><jats:bold>IMPORTANCE<\/jats:bold>The late cell division protein GpsB is important for cell wall biosynthesis in Gram-positive bacteria. GpsB of the human pathogen<jats:named-content content-type=\"genus-species\">L. monocytogenes<\/jats:named-content>interacts with one of the key enzymes of this pathway, penicillin binding protein A1 (PBP A1), and influences its activity. PBP A1 catalyzes the last two steps of cell wall biosynthesis, but it is unknown how GpsB controls PBP A1. We observed that a<jats:named-content content-type=\"genus-species\">L. monocytogenes<\/jats:named-content><jats:italic>gpsB<\/jats:italic>mutant forms spontaneous suppressors and have mapped their mutations to genes mediating and influencing the first step of cell wall biosynthesis, likely stimulating the influx of metabolites into this pathway. We assume that GpsB is important to ensure productive incorporation of cell wall precursors into the peptidoglycan sacculus by PBP A1.<\/jats:p>","DOI":"10.1128\/jb.00393-16","type":"journal-article","created":{"date-parts":[[2016,10,25]],"date-time":"2016-10-25T02:39:18Z","timestamp":1477363158000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":29,"title":["Suppressor Mutations Linking<i>gpsB<\/i>with the First Committed Step of Peptidoglycan Biosynthesis in Listeria monocytogenes"],"prefix":"10.1128","volume":"199","author":[{"given":"Jeanine","family":"Rismondo","sequence":"first","affiliation":[{"name":"FG11 Division of Enteropathogenic Bacteria and Legionella, Robert Koch Institute, Wernigerode, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer K.","family":"Bender","sequence":"additional","affiliation":[{"name":"FG13 Nosocomial Pathogens and Antibiotic Resistances, Robert Koch Institute, Wernigerode, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"Halbedel","sequence":"additional","affiliation":[{"name":"FG11 Division of Enteropathogenic Bacteria and Legionella, Robert Koch Institute, Wernigerode, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"crossref","first-page":"a000414","DOI":"10.1101\/cshperspect.a000414","article-title":"The bacterial cell envelope","volume":"2","author":"Silhavy TJ","year":"2010","unstructured":"Silhavy TJ Kahne D Walker S . 2010. The bacterial cell envelope. Cold Spring Harb Perspect Biol2:a000414.","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-micro-092412-155620"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6976.2008.00102.x"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6976.2007.00094.x"},{"key":"e_1_3_3_6_2","first-page":"21","article-title":"Lipid flippases for bacterial peptidoglycan biosynthesis","volume":"8","author":"Ruiz N","year":"2015","unstructured":"Ruiz N . 2015. Lipid flippases for bacterial peptidoglycan biosynthesis. 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