{"doi":"10.1128/iai.00442-25","title":"A zinc-free alternative ribosomal protein RpsN.2 confers survival advantage to group A streptococcus during Zn scarcity","abstract":"ABSTRACT Infection induces unfavorable environments in the host that can be detrimental to the survival of commensal and pathogenic bacteria. Although the adaptive strategies employed by pathogenic bacteria to overcome harsh environments are characterized, similar capabilities of the commensal bacteria to survive in hostile host niches during infection remain understudied. The human oral pathogen group A streptococcus (GAS) encounters host-induced zinc (Zn) limitation at infection sites that limits bacterial proliferation. However, GAS employs the Zn-sensing transcription regulator AdcR to monitor Zn levels and evades host-imposed Zn scarcity by upregulating the AdcR regulon. To elucidate the adaptive responses of oropharyngeal commensal streptococci to Zn scarcity, we analyzed the oropharyngeal pathogenic and commensal streptococcal genomes for the presence of the AdcR regulon. GAS has the full repertoire of the AdcR regulon that includes adcR , Zn importer adcABC , extracellular Zn binding proteins adcAII and Pht , and Zn-free alternative ribosomal S14 subunit, rpsN.2 . Contrarily, except for the conserved presence of adcR and adcABC , the oropharyngeal commensal streptococci varied in the composition of the AdcR regulon. Specifically, the gene encoding rpsN.2 was absent in the screened commensal streptococcal genomes. We further demonstrated that rpsN.2 is critical for the survival of GAS in Zn-limiting environments including human saliva, whereas the commensal Streptococcus vestibularis that lacks several components of the AdcR regulon, including rpsN.2 , is defective in survival in Zn-deficient conditions. Together, we identified a pathogen-specific adaptive strategy that aids evasion of host-imposed Zn limitation and confers survival advantage over oropharyngeal commensal streptococci during Zn scarcity.","journal":"Infection and Immunity","year":2025,"id":535424,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9595,"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":1419016,"name":"Aswin Thacharodi","orcid":"0000-0003-1729-4933","position":1,"is_corresponding":false},{"id":910016,"name":"Dieu Linh Nguyen","orcid":"0009-0009-7929-2192","position":2,"is_corresponding":false},{"id":486058,"name":"Nishanth Makthal","orcid":"0000-0003-3464-8537","position":3,"is_corresponding":false},{"id":1065541,"name":"Charles Bernard","orcid":"0000-0002-8354-5350","position":4,"is_corresponding":false},{"id":262649,"name":"Muthiah Kumaraswami","orcid":"0000-0002-9959-5598","position":5,"is_corresponding":false},{"id":1306137,"name":"Subhasree Saha","orcid":null,"position":0,"is_corresponding":true}],"reference_count":81,"raw_metadata":null,"created_at":"2026-07-19T02:51:56.297114Z","pmid":"41251380","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":[]}