{"doi":"10.64898/2025.12.21.695826","title":"The <i>Bacillus subtilis</i> class A penicillin-binding protein 4 (PBP4) requires an accessory protein RpdA","abstract":"PG synthesis involves class A PBPs that act independently and class B PBPs that function in complexes for cell elongation (the elongasome) and division (the divisome). Here, we identify RpdA (formerly YufK) as a specific regulator of PBP4. Inactivation of either vegetative class A PBP (PBP1 or PBP4) by the β-lactam antibiotic cefuroxime (CEF) is toxic and their loss confers CEF resistance. Similarly, loss of RpdA increases CEF resistance and genetic epistasis studies reveal that RpdA functions in a pathway with PBP4. In the absence of RpdA, PBP4 is no longer membrane localized. Analysis of a predicted RpdA-PBP4 protein complex suggests that RpdA has a second function in addition to serving as a membrane scaffold. Induction of RpdA reduces sensitivity to an undecaprenyl-phosphate binding antibiotic, consistent with a role in recycling of this important lipid carrier. We conclude that RpdA is a PBP4 accessory protein critical for its localization and activity.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":559722,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9648,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":354228,"name":"Yesha Patel","orcid":"0000-0001-9888-9888","position":1,"is_corresponding":false},{"id":338747,"name":"John D. Helmann","orcid":"0000-0002-3832-3249","position":2,"is_corresponding":false},{"id":924672,"name":"Ruoqi Huang","orcid":"0000-0002-1828-0376","position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":null,"created_at":"2026-07-19T02:55:39.010633Z","pmid":"41497608","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":[]}