Identification of potential mutations associated with multidrug resistance among isolates of Mycobacterium tuberculosis in Malaysia by in silico screening. Asia Pacific Journal of Molecular Biology and Biotechnology (APJMBB), 31 (4). pp. 49-58. ISSN 0128-7451 (2023)
Abstract
The emergence of multidrug resistance tuberculosis (MDR-TB) is caused by Mycobacterium
tuberculosis (MTB) adaptation to survive in the presence of antibiotic, that were contributed by mutations
in the MDR-associated genes. Previous research has indicated that the gene expression knockdown of
fhaA leads to an accumulation of peptidoglycan (PG) precursors at the bacillary septum and poles, which
suggest a possible deficiency in PG biosynthesis. Consequently, the cell wall becomes resistant to
antibiotics, leading to multidrug resistance (MDR). In this study, bioinformatics analyses were performed
on MDR-TB isolates from 24 clinical samples to search for novel mutations that contribute to antibiotic
resistance. We found out a potential deletion of nucleotides encoding 6 amino acids in all 12 samples,
particularly in fhaA gene (RV0020c). Our subsequent structural analysis shows that the deletion is at the
position 243-248, causing conformational change of the native FhaA protein. We postulated that the
deletion will potentially cause the loss of its binding affinity to MviN (precursor) and STPK (protein
kinase), resulting in the inhibition and blockage of the peptidoglycan polymerization, causing MDR in
MTB. In the future, experimental validation is necessitated to substantiate the association of these
mutations with MDR
| Item Type: | Article |
|---|---|
| Keywords: | Mycobacterium Tuberculosis (MTB), Antibiotic Resistance, Multidrug Resistant Tuberculosis (MDRTB), Whole Genome Sequencing (WGS) |
| Taxonomy: | By Niche > Genome > Bacterial Genomes |
| Local Content Hub: | Niche > Genome |
| Depositing User: | Hazrul Amir Tomyang (Puncak Alam) |
| Date Deposited: | 28 Mar 2025 04:19 |
| Last Modified: | 28 Mar 2025 04:19 |
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