{"doi":"10.1128/iai.01555-13","title":"CsrA (BB0184) Is Not Involved in Activation of the RpoN-RpoS Regulatory Pathway in Borrelia burgdorferi","abstract":"<jats:title>ABSTRACT</jats:title>\n          <jats:p>\n            <jats:named-content content-type=\"genus-species\">Borrelia burgdorferi</jats:named-content>\n            encodes a homologue of the bacterial carbon storage regulator A (CsrA). Recently, it was reported that CsrA contributes to\n            <jats:named-content content-type=\"genus-species\">B. burgdorferi</jats:named-content>\n            infectivity and is required for the activation of the central RpoN-RpoS regulatory pathway. However, many questions concerning the function of CsrA in\n            <jats:named-content content-type=\"genus-species\">B. burgdorferi</jats:named-content>\n            gene regulation remain unanswered. In particular, there are conflicting reports concerning the molecular details of how CsrA may modulate\n            <jats:italic>rpoS</jats:italic>\n            expression and, thus, how CsrA may influence the RpoN-RpoS pathway in\n            <jats:named-content content-type=\"genus-species\">B. burgdorferi</jats:named-content>\n            . To address these key discrepancies, we examined the role of CsrA in differential gene expression in the Lyme disease spirochete. Upon engineering an inducible\n            <jats:italic>csrA</jats:italic>\n            expression system in\n            <jats:named-content content-type=\"genus-species\">B. burgdorferi</jats:named-content>\n            , controlled hyperexpression of CsrA in a merodiploid strain did not significantly alter the protein and transcript levels of\n            <jats:italic>bosR</jats:italic>\n            ,\n            <jats:italic>rpoS</jats:italic>\n            , and RpoS-dependent genes (such as\n            <jats:italic>ospC</jats:italic>\n            and\n            <jats:italic>dbpA</jats:italic>\n            ). In addition, we constructed isogenic\n            <jats:italic>csrA</jats:italic>\n            mutants in two widely used infectious\n            <jats:named-content content-type=\"genus-species\">B. burgdorferi</jats:named-content>\n            strains. When expression of\n            <jats:italic>bosR</jats:italic>\n            ,\n            <jats:italic>rpoS</jats:italic>\n            ,\n            <jats:italic>ospC</jats:italic>\n            , and\n            <jats:italic>dbpA</jats:italic>\n            was compared between the\n            <jats:italic>csrA</jats:italic>\n            mutants and their wild-type counterparts, no detectable differences were observed. Finally, animal studies indicated that the\n            <jats:italic>csrA</jats:italic>\n            mutants remained infectious for and virulent in mice. Analyses of\n            <jats:named-content content-type=\"genus-species\">B. burgdorferi</jats:named-content>\n            gene expression in mouse tissues showed comparable levels of\n            <jats:italic>rpoS</jats:italic>\n            transcripts by the\n            <jats:italic>csrA</jats:italic>\n            mutants and the parental strains. Taken together, these results constitute compelling evidence that CsrA is not involved in activation of the RpoN-RpoS pathway and is dispensable for mammalian infectious processes carried out by\n            <jats:named-content content-type=\"genus-species\">B. burgdorferi</jats:named-content>\n            .\n          </jats:p>","journal":"Infection and Immunity","year":2014,"id":642515,"datarank":0.4566783656585135,"base_score":3.044522437723423,"endowment":3.044522437723423,"self_citation_contribution":0.4566783656585135,"citation_network_contribution":0.0,"self_endowment_contribution":0.4566783656585135,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":20,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":788665,"name":"Jianli Zhou","orcid":"0000-0001-5802-2040","position":1,"is_corresponding":false},{"id":420953,"name":"Michael V. Norgard","orcid":"0000-0002-0407-9911","position":2,"is_corresponding":false},{"id":415753,"name":"Zhiming Ouyang","orcid":"0000-0001-7427-1856","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"CsrA (BB0184) Is Not Involved in Activation of the RpoN-RpoS Regulatory Pathway in Borrelia burgdorferi","abstract":"<jats:title>ABSTRACT</jats:title>\n          <jats:p>\n            <jats:named-content content-type=\"genus-species\">Borrelia burgdorferi</jats:named-content>\n            encodes a homologue of the bacterial carbon storage regulator A (CsrA). Recently, it was reported that CsrA contributes to\n            <jats:named-content content-type=\"genus-species\">B. burgdorferi</jats:named-content>\n            infectivity and is required for the activation of the central RpoN-RpoS regulatory pathway. However, many questions concerning the function of CsrA in\n            <jats:named-content content-type=\"genus-species\">B. burgdorferi</jats:named-content>\n            gene regulation remain unanswered. In particular, there are conflicting reports concerning the molecular details of how CsrA may modulate\n            <jats:italic>rpoS</jats:italic>\n            expression and, thus, how CsrA may influence the RpoN-RpoS pathway in\n            <jats:named-content content-type=\"genus-species\">B. burgdorferi</jats:named-content>\n            . To address these key discrepancies, we examined the role of CsrA in differential gene expression in the Lyme disease spirochete. Upon engineering an inducible\n            <jats:italic>csrA</jats:italic>\n            expression system in\n            <jats:named-content content-type=\"genus-species\">B. burgdorferi</jats:named-content>\n            , controlled hyperexpression of CsrA in a merodiploid strain did not significantly alter the protein and transcript levels of\n            <jats:italic>bosR</jats:italic>\n            ,\n            <jats:italic>rpoS</jats:italic>\n            , and RpoS-dependent genes (such as\n            <jats:italic>ospC</jats:italic>\n            and\n            <jats:italic>dbpA</jats:italic>\n            ). In addition, we constructed isogenic\n            <jats:italic>csrA</jats:italic>\n            mutants in two widely used infectious\n            <jats:named-content content-type=\"genus-species\">B. burgdorferi</jats:named-content>\n            strains. When expression of\n            <jats:italic>bosR</jats:italic>\n            ,\n            <jats:italic>rpoS</jats:italic>\n            ,\n            <jats:italic>ospC</jats:italic>\n            , and\n            <jats:italic>dbpA</jats:italic>\n            was compared between the\n            <jats:italic>csrA</jats:italic>\n            mutants and their wild-type counterparts, no detectable differences were observed. Finally, animal studies indicated that the\n            <jats:italic>csrA</jats:italic>\n            mutants remained infectious for and virulent in mice. Analyses of\n            <jats:named-content content-type=\"genus-species\">B. burgdorferi</jats:named-content>\n            gene expression in mouse tissues showed comparable levels of\n            <jats:italic>rpoS</jats:italic>\n            transcripts by the\n            <jats:italic>csrA</jats:italic>\n            mutants and the parental strains. Taken together, these results constitute compelling evidence that CsrA is not involved in activation of the RpoN-RpoS pathway and is dispensable for mammalian infectious processes carried out by\n            <jats:named-content content-type=\"genus-species\">B. burgdorferi</jats:named-content>\n            .\n          </jats:p>","is_dataset_classified":null,"base_score":3.044522437723423,"endowment":3.044522437723423,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"24452681","pmcid":"PMC3993398","openalex_id":"https://openalex.org/W2167836254","authors":[],"funders":[{"funder_name":"NIAID NIH HHS","grant_id":"AI-059062","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R01 AI059062","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R56 AI059062","title":null}],"total_grants":3,"fwci":2.0125,"citation_percentile":0.85134012,"influential_citations":0,"citation_trend":[{"year":2014,"count":1},{"year":2015,"count":3},{"year":2016,"count":2},{"year":2017,"count":4},{"year":2018,"count":2},{"year":2019,"count":1},{"year":2020,"count":3},{"year":2021,"count":2},{"year":2025,"count":2}],"oa_status":"bronze","license":"https://journals.asm.org/non-commercial-tdm-license","oa_locations":[{"url":"https://iai.asm.org/content/iai/82/4/1511.full.pdf","host_type":"journal"},{"url":"https://iai.asm.org/content/iai/82/4/1511.full.pdf","host_type":"publisher"},{"url":"https://journals.asm.org/doi/pdf/10.1128/IAI.01555-13","host_type":"publisher"},{"url":"https://doi.org/10.1128/iai.01555-13","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/24452681","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3993398","host_type":"repository"}],"fields_of_study":["Vector-borne infectious diseases","Insect and Pesticide Research","Insect symbiosis and bacterial influences","Animals","Bacterial Proteins","Borrelia burgdorferi","DNA-Binding Proteins","Disease Models, Animal","Gene Expression Profiling","Gene Expression Regulation, Bacterial","Immunoblotting","Lyme Disease","Mice","RNA Polymerase Sigma 54","Real-Time Polymerase Chain Reaction","Repressor Proteins","Sigma Factor","Virulence"],"mesh_terms":["Animals","Bacterial Proteins","Disease Models, Animal","DNA-Binding Proteins","Lyme Disease","Repressor Proteins","Sigma Factor","Virulence","Immunoblotting","Gene Expression Regulation, Bacterial","Gene Expression Profiling","Borrelia burgdorferi","Mice","RNA Polymerase Sigma 54","Real-Time Polymerase Chain Reaction"],"keywords":["rpoS","Borrelia burgdorferi","Biology","rpoN","Spirochaetaceae","Mutant","Microbiology","Gene","Genetics","Gene expression","Antibody"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Clean water and sanitation"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-07T23:10:06.424590Z","pmid":null,"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":[]}