{"doi":"10.1016/j.celrep.2021.110147","title":"Thiol-based functional mimicry of phosphorylation of the two-component system response regulator ArcA promotes pathogenesis in enteric pathogens","abstract":"Pathogenic bacteria can rapidly respond to stresses such as reactive oxygen species (ROS) using reversible redox-sensitive oxidation of cysteine thiol (-SH) groups in regulators. Here, we use proteomics to profile reversible ROS-induced thiol oxidation in Vibrio cholerae, the etiologic agent of cholera, and identify two modified cysteines in ArcA, a regulator of global carbon oxidation that is phosphorylated and activated under low oxygen. ROS abolishes ArcA phosphorylation but induces the formation of an intramolecular disulfide bond that promotes ArcA-ArcA interactions and sustains activity. ArcA cysteines are oxidized in cholera patient stools, and ArcA thiol oxidation drives in vitro ROS resistance, colonization of ROS-rich guts, and environmental survival. In other pathogens, such as Salmonella enterica, oxidation of conserved cysteines of ArcA orthologs also promotes ROS resistance, suggesting a common role for ROS-induced ArcA thiol oxidation in modulating ArcA activity, allowing for a balance of expression of stress- and pathogenesis-related genetic programs.","journal":"Cell Reports","year":2021,"id":179002,"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":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9543,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":282911,"name":"Qinqin Pu","orcid":"0000-0001-8413-7802","position":1,"is_corresponding":false},{"id":506831,"name":"Jiandong Chen","orcid":"0000-0002-5144-7537","position":2,"is_corresponding":false},{"id":725667,"name":"Guijuan Hao","orcid":"0000-0003-4074-4023","position":3,"is_corresponding":false},{"id":709813,"name":"Rong Gao","orcid":"0000-0002-9245-4952","position":4,"is_corresponding":false},{"id":325233,"name":"Afsar Ali","orcid":"0009-0008-5419-1777","position":5,"is_corresponding":false},{"id":249611,"name":"Ansel Hsiao","orcid":"0000-0002-0258-6960","position":6,"is_corresponding":false},{"id":589700,"name":"Ann Stock","orcid":"0000-0002-0446-8079","position":7,"is_corresponding":false},{"id":378158,"name":"Mark Goulian","orcid":"0000-0003-0076-023X","position":8,"is_corresponding":false},{"id":321216,"name":"Jun Zhu","orcid":"0000-0001-9182-5224","position":9,"is_corresponding":false},{"id":493495,"name":"Yitian Zhou","orcid":"0000-0003-3066-5444","position":0,"is_corresponding":true}],"reference_count":91,"raw_metadata":null,"created_at":"2026-07-18T23:47:44.875897Z","pmid":"34936880","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":[]}