Project description:Related surrogate species are often used to study the molecular basis of pathogenicity of a pathogen on the basis of a shared set of biological features generally attributable to a shared core genome consisting of orthologous genes. An important and understudied aspect, however, is the extent to which regulatory features affecting the expression of such shared genes are present in both species. Here we report on an analysis of whole transcriptome maps for an important member of the TB complex Mycobacterium bovis and a closely related model organism for studying mycobacterial pathogenicity Mycobacterium marinum.
Project description:Related surrogate species are often used to study the molecular basis of pathogenicity of a pathogen on the basis of a shared set of biological features generally attributable to a shared core genome consisting of orthologous genes. An important and understudied aspect, however, is the extent to which regulatory features affecting the expression of such shared genes are present in both species. Here we report on an analysis of whole transcriptome maps for an important member of the TB complex Mycobacterium bovis and a closely related model organism for studying mycobacterial pathogenicity Mycobacterium marinum. Predict transcription start site
Project description:Mycobacterium avium subspecies paratuberculosis (MAP) is capable of causing a chronic enteritis known as Johne’s disease (JD) in ruminants, resulting in substantial economic loses. Sensitive and specific novel prognostic assays are required to help limit infection, and circulating microRNAs (miRNAs) have the potential to serve as biomarkers. Sequencing provides a thorough opportunity to characterise miRNAs but this technology is challenged by the low RNA concentrations in biofluids. The aim of this study was to determine whether small RNA-sequencing technology could be applied to bovine serum samples from an experimental JD infection model.
Project description:A comparative genomic approach was used to identify large sequence polymorphisms among Mycobacterium avium isolates obtained from a variety of host species. DNA microarrays were used as a platform for comparing mycobacteria field isolates with the sequenced bovine isolate Mycobacterium avium subsp. paratuberculosis (Map) K10. ORFs were classified as present or divergent based on the relative fluorescent intensities of the experimental samples compared to Map K10 DNA. Map isolates cultured from cattle, bison, sheep, goat, avian, and human sources were hybridized to the Map microarray. Three large deletions were observed in the genomes of four Map isolates obtained from sheep and four clusters of ORFs homologous to sequences in the Mycobacterium avium subsp. avium (Maa) 104 genome were identified as being present in these isolates. One of these clusters encodes glycopeptidolipid biosynthesis enzymes. One of the Map sheep isolates had a genome profile similar to a group of Mycobacterium avium subsp. silvaticum (Mas) isolates which included four independent laboratory stocks of the organism traditionally identified as Maa strain 18. Genome diversity in Map appears to be mostly restricted to large sequence polymorphisms that are often associated with mobile genetic elements. Keywords: Comparative genomic hybridization
Project description:Glycolipids and lipids are prominent components of bacterial cell wall that play critical roles not only in maintaining the biofilm formation but also in resistance to environmental stress. PatA is an essential membrane associated acyltransferase involved in the biosynthesis of phosphatidyl-myo-inositol mannosides (PIMs), which are the key glycolipid components in the cell wall of Mycobacterium tuberculosis. However, whether or not PatA regulates the lipids synthesis and affects drugs resistance and biofilm formation in mycobacterium is unclear, and the mechanisms involved remain to be explored. Here we show that PatA can directly regulate the synthesis of glycolipids and lipids to maintain the drugs resistance and biofilm formation in Mycobacterium smegmatis. Interestingly, the INH resistance of patA-deleted mutant is significantly enhanced although its biofilm formation is reduced. This is due to PatA negative regulation the synthesis of mycolic acids through a novel mycolic acid synthesis pathway other than the FAS pathway, which could efficiently counteract the inhibition of isoniazid on mycolic acids synthesis in mycobacterium. Furthermore, PatA is highly conserved including amino acid sequences and physiological functions in mycobacterium. Therefore, PatA regulates the synthesis of glycolipids and lipids to affect drugs resistance and biofilm formation in mycobacterium. Our findings provide a novel mycolic acids synthetic pathway and novel insights into the molecular mechanism of glycolipids and lipids metabolism regulation and their correlation with bacterial physiological phenotypes.
