{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Rivera I"],"funding":["NIAID NIH HHS","NIDCD NIH HHS","NIGMS NIH HHS"],"pagination":["2839"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6917644"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["10"],"pubmed_abstract":["Animal and human pathogens of the genus <i>Bordetella</i> are not commonly considered to be intracellular pathogens, although members of the closely related classical bordetellae are known to enter and persist within macrophages <i>in vitro</i> and have anecdotally been reported to be intracellular in clinical samples. <i>B. bronchiseptica</i>, the species closest to the ancestral lineage of the classical bordetellae, infects a wide range of mammals but is known to have an alternate life cycle, persisting, replicating and disseminating with amoeba. These observations give rise to the hypothesis that the ability for intracellular survival has an ancestral origin and is common among animal-pathogenic and environmental <i>Bordetella</i> species. Here we analyzed the survival of <i>B. bronchiseptica</i> and defined its transcriptional response to internalization by murine macrophage-like cell line RAW 264.7. Although the majority of the bacteria were killed and digested by the macrophages, a consistent fraction survived and persisted inside the phagocytes. Internalization prompted the activation of a prominent stress response characterized by upregulation of genes involved in DNA repair, oxidative stress response, pH homeostasis, chaperone functions, and activation of specific metabolic pathways. Cross species genome comparisons revealed that most of these upregulated genes are highly conserved among both the classical and non-classical <i>Bordetella</i> species. The diverse <i>Bordetella</i> species also shared the ability to survive inside RAW 264.7 cells, with the single exception being the bird pathogen <i>B. avium</i>, which has lost several of those genes. Knock-out mutations in genes expressed intracellularly resulted in decreased persistence inside the phagocytic cells, emphasizing the importance of these genes in this environment. These data show that the ability to persist inside macrophage-like RAW 264.7 cells is shared among nearly all <i>Bordetella</i> species, suggesting that resisting phagocytes may be an ancient mechanism that precedes speciation in the genus and may have facilitated the adaptation of <i>Bordetella</i> species from environmental bacteria to mammalian respiratory pathogens."],"journal":["Frontiers in microbiology"],"pubmed_title":["Conservation of Ancient Genetic Pathways for Intracellular Persistence Among Animal Pathogenic Bordetellae."],"pmcid":["PMC6917644"],"funding_grant_id":["R01 AI053075","R01 GM083113","R21 AI119787","R56 AI107016","R21 AI116186","R56 AI065507","R21 AI142678","R21 DC018496","R01 GM113681","R21 AI140399"],"pubmed_authors":["Linz B","Rivera I","Dewan KK","Ma L","Kyle DE","Rice CA","Harvill ET"],"additional_accession":[]},"is_claimable":false,"name":"Conservation of Ancient Genetic Pathways for Intracellular Persistence Among Animal Pathogenic Bordetellae.","description":"Animal and human pathogens of the genus <i>Bordetella</i> are not commonly considered to be intracellular pathogens, although members of the closely related classical bordetellae are known to enter and persist within macrophages <i>in vitro</i> and have anecdotally been reported to be intracellular in clinical samples. <i>B. bronchiseptica</i>, the species closest to the ancestral lineage of the classical bordetellae, infects a wide range of mammals but is known to have an alternate life cycle, persisting, replicating and disseminating with amoeba. These observations give rise to the hypothesis that the ability for intracellular survival has an ancestral origin and is common among animal-pathogenic and environmental <i>Bordetella</i> species. Here we analyzed the survival of <i>B. bronchiseptica</i> and defined its transcriptional response to internalization by murine macrophage-like cell line RAW 264.7. Although the majority of the bacteria were killed and digested by the macrophages, a consistent fraction survived and persisted inside the phagocytes. Internalization prompted the activation of a prominent stress response characterized by upregulation of genes involved in DNA repair, oxidative stress response, pH homeostasis, chaperone functions, and activation of specific metabolic pathways. Cross species genome comparisons revealed that most of these upregulated genes are highly conserved among both the classical and non-classical <i>Bordetella</i> species. The diverse <i>Bordetella</i> species also shared the ability to survive inside RAW 264.7 cells, with the single exception being the bird pathogen <i>B. avium</i>, which has lost several of those genes. Knock-out mutations in genes expressed intracellularly resulted in decreased persistence inside the phagocytic cells, emphasizing the importance of these genes in this environment. These data show that the ability to persist inside macrophage-like RAW 264.7 cells is shared among nearly all <i>Bordetella</i> species, suggesting that resisting phagocytes may be an ancient mechanism that precedes speciation in the genus and may have facilitated the adaptation of <i>Bordetella</i> species from environmental bacteria to mammalian respiratory pathogens.","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019","modification":"2021-03-03T08:37:54Z","creation":"2020-05-22T07:33:59Z"},"accession":"S-EPMC6917644","cross_references":{"pubmed":["31921025"],"doi":["10.3389/fmicb.2019.02839"]}}