ArticleBMC genomics2014
Disruption of Mycobacterium avium subsp. paratuberculosis-specific genes impairs in vivo fitness.
Article in BMC genomics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 22 citations in OpenAlex.
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- Global Phylogeny ofFrontiers in microbiology · 2022Article
- Identification of essential genes inFrontiers in microbiology · 2022Article
- Transposon mutagenesis in Mycobacterium kansasii links a small RNA gene to colony morphology and biofilm formation and identifies 9,885 intragenic insertions that do not compromise colony outgrowth.MicrobiologyOpen · 2020Article
- BacFITBase: a database to assess the relevance of bacterial genes during host infection.Nucleic acids research · 2020Article
- Elucidating the Regulon of a FurFrontiers in microbiology · 2020Article
- Global Assessment of Mycobacterium avium subsp.mSystems · 2019Article
- Mammalian cell entry operons; novel and major subset candidates for diagnostics with special reference toThe veterinary quarterly · 2019Review
- Pathogenesis, Molecular Genetics, and Genomics ofFrontiers in veterinary science · 2017Review
- Iron Acquisition in Mycobacterium avium subsp. paratuberculosis.Journal of bacteriology · 2015Article
- Genetic diversity of Mycobacterium avium subspecies paratuberculosis and the influence of strain type on infection and pathogenesis: a review.Veterinary research · 2015Review
- Identification of a lineage specific zinc responsive genomic island in Mycobacterium avium ssp. paratuberculosis.BMC genomics · 2014Article
- Generation and screening of a comprehensive Mycobacterium avium subsp. paratuberculosis transposon mutant bank.Frontiers in cellular and infection microbiology · 2014Article
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundMycobacterium avium subsp. paratuberculosis (MAP) is an obligate intracellular pathogen that infects many ruminant species. The acquisition of foreign genes via horizontal gene transfer has been postulated to contribute to its pathogenesis, as these genetic elements are absent from its putative ancestor, M. avium subsp. hominissuis (MAH), an environmental organism with lesser pathogenicity. In this study, high-throughput sequencing of MAP transposon libraries were analyzed to qualitatively and quantitatively determine the contribution of individual genes to bacterial survival during infection.
resultsOut of 52384 TA dinucleotides present in the MAP K-10 genome, 12607 had a MycoMarT7 transposon in the input pool, interrupting 2443 of the 4350 genes in the MAP genome (56%). Of 96 genes situated in MAP-specific genomic islands, 82 were disrupted in the input pool, indicating that MAP-specific genomic regions are dispensable for in vitro growth (odds ratio = 0.21). Following 5 independent in vivo infections with this pool of mutants, the correlation between output pools was high for 4 of 5 (R = 0.49 to 0.61) enabling us to define genes whose disruption reproducibly reduced bacterial fitness in vivo. At three different thresholds for reduced fitness in vivo, MAP-specific genes were over-represented in the list of predicted essential genes. We also identified additional genes that were severely depleted after infection, and several of them have orthologues that are essential genes in M. tuberculosis.
conclusionsThis work indicates that the genetic elements required for the in vivo survival of MAP represent a combination of conserved mycobacterial virulence genes and MAP-specific genes acquired via horizontal gene transfer. In addition, the in vitro and in vivo essential genes identified in this study may be further characterized to offer a better understanding of MAP pathogenesis, and potentially contribute to the discovery of novel therapeutic and vaccine targets.
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