{"entity": "researcher", "timestamp": "2026-08-20T20:37:02.161Z", "family": "Fumeaux", "given": "Coralie", "initials": "C", "orcid": "0000-0002-6969-3111", "affiliations": ["Institute of Microbiology, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland"], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/34711f3602884fd690fdb859dae1cc8e.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/34711f3602884fd690fdb859dae1cc8e"}}, "publications": [{"entity": "publication", "iuid": "e9079cc7a5264f278ff6c99d7f6c6346", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/e9079cc7a5264f278ff6c99d7f6c6346.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/e9079cc7a5264f278ff6c99d7f6c6346"}}, "title": "Disruption of undecaprenyl phosphate recycling suppresses ampC beta-lactamase induction in Pseudomonas aeruginosa.", "authors": [{"family": "Klycheva", "given": "Karina", "initials": "K"}, {"family": "Gyger", "given": "Jo\u00ebl", "initials": "J"}, {"family": "Frund", "given": "M\u00e9lissa", "initials": "M"}, {"family": "Torrens", "given": "Gabriel", "initials": "G"}, {"family": "Cava", "given": "Felipe", "initials": "F"}, {"family": "Fumeaux", "given": "Coralie", "initials": "C", "orcid": "0000-0002-6969-3111", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/34711f3602884fd690fdb859dae1cc8e.json"}}], "type": "journal article", "published": "2025-10-00", "journal": {"title": "PLoS Pathog", "issn": "1553-7374", "volume": "21", "issue": "10", "pages": "e1013633", "issn-l": "1553-7366"}, "abstract": "Beta-lactam antibiotics are widely used to treat bacterial infections, but their efficacy is compromised by resistance mechanisms such as the production of beta-lactamases. In Pseudomonas aeruginosa, the chromosomally encoded beta-lactamase AmpC is the primary mediator of beta-lactam resistance. ampC expression is regulated by the transcription factor AmpR, which responds to intracellular peptidoglycan (PG) fragments. Under normal conditions, AmpR binds the PG precursor (UDP-MurNAc-pentapeptide) and represses ampC expression. However, during beta-lactam treatment or in PG recycling-deficient mutants such as ampD mutants, PG degradation products (anhydromuropeptides) accumulate and activate AmpR, resulting in elevated ampC expression and beta-lactam resistance. We hypothesized that shifting the balance of PG precursors could modulate AmpR activity and suppress beta-lactamase expression, even in derepressed strains. Undecaprenyl phosphate (UndP) is a lipid carrier essential for translocating PG precursors across the bacterial inner membrane. Recent work has identified members of the DedA superfamily as UndP flippases responsible for recycling this lipid carrier. Disruption of UndP recycling leads to cytoplasmic accumulation of UDP-MurNAc-pentapeptide, the known AmpR repressor. Here, we show that deletion of dedA4, which encodes a predicted UndP flippase in P. aeruginosa, causes PG precursors accumulation and significantly reduces AmpC production and beta-lactam resistance in an ampD mutant. These findings highlight the influence of PG precursor dynamics on beta-lactamase regulation and identify DedA4 as a promising therapeutic target. Inhibiting UndP recycling offers a novel strategy to counteract beta-lactam resistance in P. aeruginosa and potentially other AmpC-producing pathogens.", "doi": "10.1371/journal.ppat.1013633", "pmid": "41118418", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC12561984"}, {"db": "pii", "key": "PPATHOGENS-D-25-01415"}], "notes": [], "created": "2026-08-20T12:44:59.313Z", "modified": "2026-08-20T12:44:59.373Z"}, {"entity": "publication", "iuid": "ebdcfc0ede674ee9b8f98c185eaf36aa", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/ebdcfc0ede674ee9b8f98c185eaf36aa.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/ebdcfc0ede674ee9b8f98c185eaf36aa"}}, "title": "Disruption of undecaprenyl phosphate recycling suppresses ampC beta-lactamase induction in Pseudomonas aeruginosa", "authors": [{"family": "Klycheva", "given": "Karina", "initials": "K"}, {"family": "Gyger", "given": "Jo\u00ebl", "initials": "J"}, {"family": "Frund", "given": "M\u00e9lissa", "initials": "M"}, {"family": "Torrens", "given": "Gabriel", "initials": "G"}, {"family": "Cava", "given": "Felipe", "initials": "F", "orcid": "0000-0001-5995-718X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/bbcff12a06814d54afea533e125a1213.json"}}, {"family": "Fumeaux", "given": "Coralie", "initials": "C", "orcid": "0000-0002-6969-3111", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/34711f3602884fd690fdb859dae1cc8e.json"}}], "type": "posted-content", "published": "2025-06-05", "journal": {"issn-l": null}, "abstract": null, "doi": "10.1101/2025.06.03.657773", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T11:06:00.899Z", "modified": "2026-08-20T11:06:00.951Z"}, {"entity": "publication", "iuid": "7d1b9ef2c00c47b9b508ee060129596d", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/7d1b9ef2c00c47b9b508ee060129596d.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/7d1b9ef2c00c47b9b508ee060129596d"}}, "title": "A potential space-making role in cell wall biogenesis for SltB1and DacB revealed by a beta-lactamase induction phenotype in Pseudomonas aeruginosa.", "authors": [{"family": "Gyger", "given": "Jo\u00ebl", "initials": "J"}, {"family": "Torrens", "given": "Gabriel", "initials": "G"}, {"family": "Cava", "given": "Felipe", "initials": "F", "orcid": "0000-0001-5995-718X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/bbcff12a06814d54afea533e125a1213.json"}}, {"family": "Bernhardt", "given": "Thomas G", "initials": "TG", "orcid": "0000-0003-3566-7756", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ea73f668f266458f84121087f7b732cc.json"}}, {"family": "Fumeaux", "given": "Coralie", "initials": "C", "orcid": "0000-0002-6969-3111", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/34711f3602884fd690fdb859dae1cc8e.json"}}], "type": "journal article", "published": "2024-07-17", "journal": {"title": "MBio", "issn": "2150-7511", "volume": "15", "issue": "7", "pages": "e0141924", "issn-l": null}, "abstract": "Pseudomonas aeruginosa encodes the beta-lactamase AmpC, which promotes resistance to beta-lactam antibiotics. Expression of ampC 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 dacB occur in beta-lactam-resistant clinical isolates of P. aeruginosa, but it has remained unclear why DacB inactivation promotes ampC induction. Similarly, the inactivation of lytic transglycosylase (LT) enzymes such as SltB1 that cut PG glycans has also been associated with ampC induction and beta-lactam resistance. Given that LT enzymes are capable of producing AMP products that serve as ampC inducers, this latter observation has been especially difficult to explain. Here, we show that ampC induction in sltB1 or dacB mutants requires another LT enzyme called MltG. In Escherichia coli, MltG has been implicated in the degradation of nascent PG strands produced upon beta-lactam treatment. Accordingly, in P. aeruginosa sltB1 and dacB 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 ampC-inducing signal.\n\nInducible beta-lactamases like the ampC system of Pseudomonas aeruginosa are a common determinant of beta-lactam resistance among gram-negative bacteria. The regulation of ampC is elegantly tuned to detect defects in cell wall synthesis caused by beta-lactam drugs. Studies of mutations causing ampC 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 ampC 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.", "doi": "10.1128/mbio.01419-24", "pmid": "38920394", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC11253642"}], "notes": [], "created": "2026-08-20T12:00:28.713Z", "modified": "2026-08-20T12:00:28.846Z"}]}