{"doi":"10.1128/mbio.02708-23","title":"Evidence for Rho-dependent control of a virulence switch in <i>Acinetobacter baumannii</i>","abstract":"ABSTRACT Acinetobacter baumannii strain AB5075 is able to interconvert at high frequency between virulent cells that form opaque colonies (VIR-O) and avirulent cells that form translucent colonies (AV-T). Cells switch from the VIR-O to the AV-T state by the combinatorial activation of at least three TetR-type transcriptional regulators (TTTRs). A genetic screen identified the transcription termination factor Rho as a major contributor that controls expression differences of these TTTRs between VIR-O and AV-T cells. Each TTTR has a long mRNA leader region where transcripts are terminated in VIR-O cells. However, in AV-T cells, the degree of termination in each TTTR leader was greatly reduced, allowing for higher levels of TTTR expression. In a strain with decreased Rho expression, or in wild-type VIR-O cells treated with the Rho inhibitor bicyclomycin, the degree of termination in each TTTR mRNA leader region was reduced. Mutations in the leader region of one TTTR, ABUW_1645 , were identified that reduced the degree of termination. Purified Rho protein bound the leader region of the most frequently activated TTTR ABUW_1645 and the least frequently activated TTTR ABUW_1959 with similar affinities. This together with the observation that the levels of Rho protein were unchanged between VIR-O and AV-T cells, suggested that additional factors differentially modulate Rho activity between each variant. Finally, we demonstrate in AV-T cells that nutrient depletion is a condition that increases the levels of Rho-dependent transcription termination in the TTTR leader regions to regulate this phenotypic switch. IMPORTANCE Acinetobacter baumannii is a significant cause of infections in the healthcare setting. More recently, A. baumannii has been a leading cause of secondary bacterial pneumonia in patients infected with SARS-CoV-2 and the overall frequency of A. baumannii infection increased 78% during the COVID-19 pandemic. A. baumannii can exist in virulent or avirulent subpopulations and this interconversion is mediated by the expression of a family of TetR-type transcriptional regulators. In this study, we demonstrate that Rho is a key regulatory component in the expression of these TetR regulators. Overall, this study is the first to address a role for Rho in A. baumannii and provides additional evidence for the role of Rho in regulating diversity in bacterial subpopulations.","journal":"mBio","year":2023,"id":364969,"datarank":0.42260326635818923,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"self_citation_contribution":0.31191623125197543,"citation_network_contribution":0.11068703510621382,"self_endowment_contribution":0.31191623125197543,"citer_contribution":0.11068703510621382,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":4,"citers_with_citation_signal":4,"citers_with_endowment":4,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9574,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1120517,"name":"Raja Singh","orcid":null,"position":1,"is_corresponding":false},{"id":272342,"name":"Jennifer M. Colquhoun","orcid":"0000-0002-2659-2919","position":2,"is_corresponding":false},{"id":1120518,"name":"Olivia G. Starich","orcid":null,"position":3,"is_corresponding":false},{"id":491456,"name":"Aimee R. P. Tierney","orcid":null,"position":4,"is_corresponding":false},{"id":907456,"name":"Kyle A. Tipton","orcid":null,"position":5,"is_corresponding":false},{"id":272343,"name":"Philip N. Rather","orcid":"0000-0001-9674-6250","position":6,"is_corresponding":false},{"id":490737,"name":"María Pérez−Varela","orcid":"0000-0003-0990-4041","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:14:41.218128Z","pmid":"38085026","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":[]}