{"entity": "researcher", "timestamp": "2026-08-20T20:46:00.658Z", "family": "Bernhardt", "given": "Thomas G", "initials": "TG", "orcid": "0000-0003-3566-7756", "affiliations": ["Howard Hughes Medical Institute, Chevy Chase, Maryland, USA.", "Department of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts, USA."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/ea73f668f266458f84121087f7b732cc.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/ea73f668f266458f84121087f7b732cc"}}, "publications": [{"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"}, {"entity": "publication", "iuid": "3195ab9977a6442b8fbfb43653c315f6", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/3195ab9977a6442b8fbfb43653c315f6.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/3195ab9977a6442b8fbfb43653c315f6"}}, "title": "MacP bypass variants of Streptococcus pneumoniae PBP2a suggest a conserved mechanism for the activation of bifunctional cell wall synthases.", "authors": [{"family": "Midonet", "given": "Caroline", "initials": "C"}, {"family": "Bisset", "given": "Sean", "initials": "S"}, {"family": "Shlosman", "given": "Irina", "initials": "I"}, {"family": "Cava", "given": "Felipe", "initials": "F", "orcid": "0000-0001-5995-718X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/bbcff12a06814d54afea533e125a1213.json"}}, {"family": "Rudner", "given": "David Z", "initials": "DZ", "orcid": "0000-0002-0236-7143", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f12d8cd1d4644e5fa000b30b91cd7ee1.json"}}, {"family": "Bernhardt", "given": "Thomas G", "initials": "TG", "orcid": "0000-0003-3566-7756", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ea73f668f266458f84121087f7b732cc.json"}}], "type": "journal article", "published": "2023-12-19", "journal": {"title": "MBio", "issn": "2150-7511", "volume": "14", "issue": "6", "pages": "e0239023", "issn-l": null}, "abstract": "Class A penicillin-binding proteins (aPBPs) play critical roles in bacterial cell wall biogenesis. As the targets of penicillin, they are among the most important drug targets in history. Although the biochemical activities of these enzymes have been well studied, little is known about how they are regulated in cells to control when and where peptidoglycan is made. In this report, we isolate variants of the Streptococcus pneumoniae enzyme PBP2a that function in cells without MacP, a partner normally required for its activity. The amino acid substitutions activate the cell wall synthase activity of PBP2a, and their location in a model structure suggests an activation mechanism for this enzyme that is shared with aPBPs from distantly related organisms with distinct activators.", "doi": "10.1128/mbio.02390-23", "pmid": "37847021", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC10746261"}], "notes": [], "created": "2026-08-20T12:00:37.188Z", "modified": "2026-08-20T12:00:37.297Z"}]}