{"doi":"10.1128/mbio.01793-21","title":"Penicillanic Acid Sulfones Inactivate the Extended-Spectrum β-Lactamase CTX-M-15 through Formation of a Serine-Lysine Cross-Link: an Alternative Mechanism of β-Lactamase Inhibition","abstract":", preventing effective treatment with most penicillins and cephalosporins. Combining β-lactams with β-lactamase inhibitors (BLIs) is a validated route to overcome such resistance. Here, we describe how exposure to enmetazobactam and tazobactam, BLIs based on a penicillanic acid sulfone (PAS) scaffold, leads to a protein modification in CTX-M-15, resulting in irremediable inactivation of this most commonly encountered member of the CTX-M family. High-resolution X-ray crystal structures showed that PAS exposure induces formation of a cross-link between Ser70 and Lys73, two residues critical to β-lactamase function. This previously undescribed mechanism of inhibition furthers our understanding of β-lactamase inhibition by classical PAS inhibitors and provides a basis for further, rational inhibitor development.","journal":"mBio","year":2022,"id":258688,"datarank":0.4335557636844247,"base_score":2.8903717578961645,"endowment":2.8903717578961645,"self_citation_contribution":0.4335557636844247,"citation_network_contribution":0.0,"self_endowment_contribution":0.4335557636844247,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":17,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9572,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":354485,"name":"Catherine L. Tooke","orcid":"0000-0003-2180-3235","position":1,"is_corresponding":false},{"id":384425,"name":"Christopher R. Bethel","orcid":null,"position":2,"is_corresponding":false},{"id":293631,"name":"Benlian Wang","orcid":null,"position":3,"is_corresponding":false},{"id":910270,"name":"Christopher J. Arthur","orcid":"0000-0001-7577-8472","position":4,"is_corresponding":false},{"id":483205,"name":"Kate J. Heesom","orcid":"0000-0002-5418-5392","position":5,"is_corresponding":false},{"id":910271,"name":"Stuart Shapiro","orcid":"0000-0002-4837-7638","position":6,"is_corresponding":false},{"id":250427,"name":"Daniela Schlatzer","orcid":"0000-0001-7151-594X","position":7,"is_corresponding":false},{"id":270505,"name":"Krisztina M. Papp‐Wallace","orcid":"0000-0002-9976-7898","position":8,"is_corresponding":false},{"id":232761,"name":"Robert A. Bonomo","orcid":"0000-0002-3299-894X","position":9,"is_corresponding":false},{"id":354489,"name":"James Spencer","orcid":"0000-0002-4602-0571","position":10,"is_corresponding":false},{"id":354486,"name":"Philip Hinchliffe","orcid":"0000-0001-8611-4743","position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:25:43.037820Z","pmid":"35612361","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}