ArticlePloS one2012
Phenotypic and transcriptomic response of auxotrophic Mycobacterium avium subsp. paratuberculosis leuD mutant under environmental stress.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 22 citations in OpenAlex.
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- Pathogenesis, Molecular Genetics, and Genomics ofFrontiers in veterinary science · 2017Review
- High-Throughput Carbon Substrate Profiling of Mycobacterium ulcerans Suggests Potential Environmental Reservoirs.PLoS neglected tropical diseases · 2017Article
- Article
- Comparative genomic and phenomic analysis of Clostridium difficile and Clostridium sordellii, two related pathogens with differing host tissue preference.BMC genomics · 2015Article
- Identifying feasible metabolic routes in Mycobacterium smegmatis and possible alterations under diverse nutrient conditions.BMC microbiology · 2014Article
- Comparative nutritional and chemical phenome of Clostridium difficile isolates determined using phenotype microarrays.International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases · 2014Article
- Generation and screening of a comprehensive Mycobacterium avium subsp. paratuberculosis transposon mutant bank.Frontiers in cellular and infection microbiology · 2014Article
- Screening of Mycobacterium avium subsp. paratuberculosis mutants for attenuation in a bovine monocyte-derived macrophage model.Frontiers in cellular and infection microbiology · 2014Article
- The MetaCyc database of metabolic pathways and enzymes and the BioCyc collection of Pathway/Genome Databases.Nucleic acids research · 2014Article
- Evaluation of a Mycobacterium avium subsp. paratuberculosis leuD mutant as a vaccine candidate against challenge in a caprine model.Clinical and vaccine immunology : CVI · 2013Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of severe gastroenteritis in cattle. To gain a better understanding of MAP virulence, we investigated the role of leuD gene in MAP metabolism and stress response. For this, we have constructed an auxotrophic strain of MAP by deleting the leuD gene using allelic exchange. The wildtype and mutant strains were then compared for metabolic phenotypic changes using Biolog phenotype microarrays. The responses of both strains to physiologically relevant stress conditions were assessed using DNA microarrays. Transcriptomic data was then analyzed in the context of cellular metabolic pathways and gene networks. Our results showed that deletion of leuD gene has a global effect on both MAP phenotypic and transcriptome response. At the metabolic level, the mutant strain lost the ability to utilize most of the carbon, nitrogen, sulphur, phosphorus and nutrient supplements as energy source. At the transcriptome level, more than 100 genes were differentially expressed in each of the stress condition tested. Systems level network analysis revealed that the differentially expressed genes were distributed throughout the gene network, thus explaining the global impact of leuD deletion in metabolic phenotype. Further, we find that leuD deletion impacted metabolic pathways associated with fatty acids. We verified this by experimentally estimating the total fatty acid content of both mutant and wildtype. The mutant strain had 30% less fatty acid content when compared to wildtype, thus supporting the results from transcriptional and computational analyses. Our results therefore reveal the intricate connection between the metabolism and virulence in MAP.
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