Dataset Information

Conservation of Ancient Genetic Pathways for Intracellular Persistence Among Animal Pathogenic Bordetellae.

ABSTRACT: Animal and human pathogens of the genus Bordetella are not commonly considered to be intracellular pathogens, although members of the closely related classical bordetellae are known to enter and persist within macrophages in vitro and have anecdotally been reported to be intracellular in clinical samples. B. bronchiseptica, 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 Bordetella species. Here we analyzed the survival of B. bronchiseptica 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 Bordetella species. The diverse Bordetella species also shared the ability to survive inside RAW 264.7 cells, with the single exception being the bird pathogen B. avium, 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 Bordetella species, suggesting that resisting phagocytes may be an ancient mechanism that precedes speciation in the genus and may have facilitated the adaptation of Bordetella species from environmental bacteria to mammalian respiratory pathogens.

SUBMITTER: Rivera I

PROVIDER: S-EPMC6917644 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Conservation of Ancient Genetic Pathways for Intracellular Persistence Among Animal Pathogenic Bordetellae.

Rivera Israel I Linz Bodo B Dewan Kalyan K KK Ma Longhuan L Rice Christopher A CA Kyle Dennis E DE Harvill Eric T ET

Frontiers in microbiology 20191211

Animal and human pathogens of the genus Bordetella are not commonly considered to be intracellular pathogens, although members of the closely related classical bordetellae are known to enter and persist within macrophages in vitro and have anecdotally been reported to be intracellular in clinical samples. B. bronchiseptica, 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, ...[more]

PMID: 31921025

Similar Datasets

Project description:Increasing experimental evidence supports that Mycobacterium tuberculosis (Mtb) has evolved strategies to survive within the lysosomes from activated macrophages, which may represent a reservoir for persistent mycobacteria. To further our knowledge in Mtb response to the lysosomal environment, we profiled the global transcriptional activity of Mtb in a lysosomal in vitro exposure (LivE) model. At inhibitory conditions of lysosomal SF (iLivE), which did not kill but arrested mycobacterial replication thereby mimicking persistence, Mtb expresses a unique transcriptome, where genes involved in general stress response, metabolic reprogramming, cell wall remodeling, respiration, oxidative stress and dormancy response were found to be significantly modulated. Genes encoding for protein families involved in Mtb virulence including ESAT-6, PE-PPE and Mce proteins were also distinctly regulated. Extensive meta-analysis of the Mtb transcriptomes from iLivE and previously reported ex vivo, in vivo and in vitro stress models revealed most significant overlap between iLivE and primary murine macrophage infection model. Our study also highlighted the α-glucan synthesis pathway and a distinct set of toxin-antitoxin systems as toxicity mechanisms that could be exploited as novel antimicrobial approaches for intra-macrophage persistent bacilli. The specificity in responses generated in the LivE model was supported by the significant number of iLivE genes that did not overlap with any of the previously reported in vitro stress models. Finally, to validate the relevance of the LivE model, rv1258c encoding for the efflux pump protein Tap, was selected from the iLivE Mtb transcriptome for further characterization. An Mtb Δrv1258c mutant was constructed and displayed increased susceptibility to killing by lysosomal SF and by the antimicrobial peptide LL-37 found in lysosomes. Furthermore, Δrv1258c Mtb was attenuated in its ability to survive in primary murine macrophages.

Dataset Information

Conservation of Ancient Genetic Pathways for Intracellular Persistence Among Animal Pathogenic Bordetellae.

Publications

Conservation of Ancient Genetic Pathways for Intracellular Persistence Among Animal Pathogenic Bordetellae.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets