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Expression of\n                      <jats:italic>ampC<\/jats:italic>\n                      is induced by anhydro-muropeptides (AMPs) released from the peptidoglycan (PG) cell wall upon beta-lactam treatment. AmpC can also be induced via genetic inactivation of PG biogenesis factors such as the endopeptidase DacB that cleaves PG crosslinks. Mutants in\n                      <jats:italic>dacB<\/jats:italic>\n                      occur in beta-lactam-resistant clinical isolates of\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      , but it has remained unclear why DacB inactivation promotes\n                      <jats:italic>ampC<\/jats:italic>\n                      induction. Similarly, the inactivation of lytic transglycosylase (LT) enzymes such as SltB1 that cut PG glycans has also been associated with\n                      <jats:italic>ampC<\/jats:italic>\n                      induction and beta-lactam resistance. Given that LT enzymes are capable of producing AMP products that serve as\n                      <jats:italic>ampC<\/jats:italic>\n                      inducers, this latter observation has been especially difficult to explain. Here, we show that\n                      <jats:italic>ampC<\/jats:italic>\n                      induction in\n                      <jats:italic>sltB1<\/jats:italic>\n                      or\n                      <jats:italic>dacB<\/jats:italic>\n                      mutants requires another LT enzyme called MltG. In\n                      <jats:italic>Escherichia coli<\/jats:italic>\n                      , MltG has been implicated in the degradation of nascent PG strands produced upon beta-lactam treatment. Accordingly, in\n                      <jats:italic>P. aeruginosa sltB1<\/jats:italic>\n                      and\n                      <jats:italic>dacB<\/jats:italic>\n                      mutants, we detected the MltG-dependent production of pentapeptide-containing AMP products that are signatures of nascent PG degradation. Our results therefore support a model in which SltB1 and DacB use their PG-cleaving activity to open space in the PG matrix for the insertion of new material. Thus, their inactivation mimics low-level beta-lactam treatment by reducing the efficiency of new PG insertion into the wall, causing the degradation of some nascent PG material by MltG to produce the\n                      <jats:italic>ampC<\/jats:italic>\n                      -inducing signal.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      Inducible beta-lactamases like the ampC system of\n                      <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                      are a common determinant of beta-lactam resistance among gram-negative bacteria. The regulation of\n                      <jats:italic>ampC<\/jats:italic>\n                      is elegantly tuned to detect defects in cell wall synthesis caused by beta-lactam drugs. Studies of mutations causing\n                      <jats:italic>ampC<\/jats:italic>\n                      induction in the absence of drug therefore promise to reveal new insights into the process of cell wall biogenesis in addition to aiding our understanding of how resistance to beta-lactam antibiotics arises in the clinic. In this study, the\n                      <jats:italic>ampC<\/jats:italic>\n                      induction phenotype for mutants lacking a glycan-cleaving enzyme or an enzyme that cuts cell wall crosslinks was used to uncover a potential role for these enzymes in making space in the wall matrix for the insertion of new material during cell growth.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.01419-24","type":"journal-article","created":{"date-parts":[[2024,6,26]],"date-time":"2024-06-26T09:02:48Z","timestamp":1719392568000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":9,"title":["A potential space-making role in cell wall biogenesis for SltB1and DacB revealed by a beta-lactamase induction phenotype in\n                    <i>Pseudomonas aeruginosa<\/i>"],"prefix":"10.1128","volume":"15","author":[{"given":"Jo\u00ebl","family":"Gyger","sequence":"first","affiliation":[{"name":"Institute of Microbiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Torrens","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Infection Medicine Sweden (MIMS), Ume\u00e5 Center for Microbial Research (UCMR), Umea, Sweden"},{"name":"Department of Molecular Biology, Science for Life Laboratory (SciLifeLab), Ume\u00e5 University, Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5995-718X","authenticated-orcid":true,"given":"Felipe","family":"Cava","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Infection Medicine Sweden (MIMS), Ume\u00e5 Center for Microbial Research (UCMR), Umea, Sweden"},{"name":"Department of 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