Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Viswanathan, G; Joshi, SV; Sridhar, A; Dutta, S; Raghunand, TR.
Identifying novel mycobacterial stress associated genes using a random mutagenesis screen in Mycobacterium smegmatis.
Gene. 2015; 574(1): 20-7.
Doi: 10.1016/j.gene.2015.07.063
Web of Science
PubMed
FullText
FullText_MUG
- Co-Autor*innen der Med Uni Graz
- Dutta Sayantanee
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- Cell envelope associated components of Mycobacterium tuberculosis (M.tb) have been implicated in stress response, immune modulation and in vivo survival of the pathogen. Although many such factors have been identified, there is a large disparity between the number of genes predicted to be involved in functions linked to the envelope and those described in the literature. To identify and characterise novel stress related factors associated with the mycobacterial cell envelope, we isolated colony morphotype mutants of Mycobacterium smegmatis (M. smegmatis), based on the hypothesis that mutants with unusual colony morphology may have defects in the biosynthesis of cell envelope components. On testing their susceptibility to stress conditions relevant to M.tb physiology, multiple mutants were found to be sensitive to Isoniazid, Diamide and H2O2, indicative of altered permeability due to changes in cell envelope composition. Two mutants showed defects in biofilm formation implying possible roles for the target genes in antibiotic tolerance and/or virulence. These assays identified novel stress associated roles for several mycobacterial genes including sahH, tatB and aceE. Complementation analysis of selected mutants with the M. smegmatis genes and their M.tb homologues showed phenotypic restoration, validating their link to the observed phenotypes. A mutant carrying an insertion in fhaA encoding a forkhead associated domain containing protein, showed reduced survival in THP-1 macrophages, providing in vivo validation to this screen. Taken together, these results suggest that the M.tb homologues of a majority of the identified genes may play significant roles in the pathogenesis of tuberculosis.
- Find related publications in this database (using NLM MeSH Indexing)
- Bacterial Proteins - genetics
- Biofilms - growth & development
- Cell Wall - drug effects, genetics
- Gene Expression Regulation, Bacterial - drug effects, genetics
- Genes, Bacterial - genetics
- Hydrogen Peroxide - pharmacology
- Macrophages - drug effects
- Mutagenesis - genetics
- Mutation - genetics
- Mycobacterium smegmatis - drug effects, genetics
- Stress, Physiological - drug effects, genetics
- Find related publications in this database (Keywords)
- Mycobacterium tuberculosis
- Mycobacterium smegmatis
- Transposon mutagenesis
- Cell envelope
- Stress susceptibility
- Biofilm formation