{"doi":"10.1111/mmi.14225","title":"Maintenance of the virulence plasmid in <i>Shigella flexneri</i> is influenced by Lon and two functional partitioning systems","abstract":"<jats:title>Summary</jats:title><jats:p>Members of the genus <jats:italic>Shigella </jats:italic>carry a large plasmid, pINV, which is essential for virulence. In <jats:italic>Shigella flexneri</jats:italic>, pINV harbours three toxin‐antitoxin (TA) systems, CcdAB, GmvAT and VapBC that promote vertical transmission of the plasmid. Type II TA systems, such as those on pINV, consist of a toxic protein and protein antitoxin. Selective degradation of the antitoxin by proteases leads to the unopposed action of the toxin once genes encoding a TA system have been lost, such as following failure to inherit a plasmid harbouring a TA system. Here, we investigate the role of proteases in the function of the pINV TA systems and demonstrate that Lon, but not ClpP, is required for their activity during plasmid stability. This provides the first evidence that acetyltransferase family TA systems, such as GmvAT, can be regulated by Lon. Interestingly, <jats:italic>S. flexneri</jats:italic> pINV also harbours two putative partitioning systems, ParAB and StbAB. We show that both systems are functional for plasmid maintenance although their activity is masked by other systems on pINV. Using a model vector based on the pINV replicon, we observe temperature‐dependent differences between the two partitioning systems that contribute to our understanding of the maintenance of virulence in <jats:italic>Shigella</jats:italic> species.</jats:p>","journal":"Molecular Microbiology","year":2019,"id":608155,"datarank":0.4887144807032224,"base_score":3.258096538021482,"endowment":3.258096538021482,"self_citation_contribution":0.4887144807032224,"citation_network_contribution":0.0,"self_endowment_contribution":0.4887144807032224,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":25,"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":1561800,"name":"Sarah Hollingshead","orcid":null,"position":1,"is_corresponding":false},{"id":772560,"name":"Giulia Pilla","orcid":"0000-0003-2315-7097","position":2,"is_corresponding":false},{"id":294747,"name":"Christoph M. 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Selective degradation of the antitoxin by proteases leads to the unopposed action of the toxin once genes encoding a TA system have been lost, such as following failure to inherit a plasmid harbouring a TA system. Here, we investigate the role of proteases in the function of the pINV TA systems and demonstrate that Lon, but not ClpP, is required for their activity during plasmid stability. This provides the first evidence that acetyltransferase family TA systems, such as GmvAT, can be regulated by Lon. Interestingly, <jats:italic>S. flexneri</jats:italic> pINV also harbours two putative partitioning systems, ParAB and StbAB. We show that both systems are functional for plasmid maintenance although their activity is masked by other systems on pINV. Using a model vector based on the pINV replicon, we observe temperature‐dependent differences between the two partitioning systems that contribute to our understanding of the maintenance of virulence in <jats:italic>Shigella</jats:italic> species.</jats:p>","is_dataset_classified":null,"base_score":3.258096538021482,"endowment":3.258096538021482,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"30767313","pmcid":"PMC6519299","openalex_id":"https://openalex.org/W2914415623","authors":[],"funders":[{"funder_name":"Wellcome Trust","grant_id":"102908/Z/13/Z","title":null},{"funder_name":"Medical Research Council","grant_id":"1808814","title":null},{"funder_name":"Wellcome Trust","grant_id":"102908","title":"Bacterial immune evasion."},{"funder_name":"Wellcome Trust","grant_id":"unidentified","title":"unidentified"},{"funder_name":"Wellcome Trust","grant_id":"","title":null},{"funder_name":"Wellcome Trust","grant_id":"","title":null}],"total_grants":6,"fwci":1.5215,"citation_percentile":0.78781444,"influential_citations":0,"citation_trend":[{"year":2020,"count":4},{"year":2021,"count":1},{"year":2022,"count":4},{"year":2023,"count":2},{"year":2024,"count":6},{"year":2025,"count":7},{"year":2026,"count":1}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/mmi.14225","host_type":"journal"},{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/mmi.14225","host_type":"publisher"},{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fmmi.14225","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1111/mmi.14225","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/full-xml/10.1111/mmi.14225","host_type":"publisher"},{"url":"https://doi.org/10.1111/mmi.14225","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/30767313","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/6519299","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC6519299","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC6519299?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.1111/mmi.14225","host_type":""},{"url":"https://irep.ntu.ac.uk/id/eprint/35894/7/13421_a1384_McVicker.pdf","host_type":""},{"url":"https://dx.doi.org/10.1111/mmi.14225","host_type":""},{"url":"https://ora.ox.ac.uk/objects/uuid:fa85c076-886c-4224-a6fb-16a52dc382f5","host_type":""}],"fields_of_study":["Escherichia coli research studies","Bacterial Genetics and Biotechnology","Salmonella and Campylobacter epidemiology","0301 basic medicine","0303 health sciences","03 medical and health sciences","Acetyltransferases","Bacterial Proteins","Escherichia coli","Escherichia coli Proteins","Gene Expression Regulation, Bacterial","Plasmids","Protease La","Replicon","Shigella flexneri","Temperature","Toxin-Antitoxin Systems","Virulence"],"mesh_terms":["Toxin-Antitoxin Systems","Acetyltransferases","Bacterial Proteins","Escherichia coli","Plasmids","Replicon","Shigella flexneri","Temperature","Virulence","Gene Expression Regulation, Bacterial","Escherichia coli Proteins","Protease La"],"keywords":["Biology","Shigella flexneri","Plasmid","Replicon","Antitoxin","Virulence","Microbiology","Genetics","Shigella","Proteases","Gene","Escherichia coli","Toxin","Enzyme","Protease La","Escherichia coli Proteins","Temperature","Toxin-Antitoxin Systems","Gene Expression Regulation, Bacterial","Bacterial Proteins","Acetyltransferases","Research Articles","Plasmids"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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