In Silico Screening For The Identification And Characterization Of Potential Mutations That Confer To Antibiotic Resistance In Malaysian Mdr-Tb Isolates

The emergence of multidrug resistance tuberculosis (MDR-TB) is caused by the adaptation of Mycobacterium tuberculosis to survive in the presence of antibiotic, which is also contributed by mutations in the MDR-associated genes. Previous studies showed that the knockdown of fhaA gene expression led t...

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Main Author:	Teh, Hui Wen
Format:	Thesis
Language:	English
Published:	2023
Subjects:	R5-920 Medicine (General)
Online Access:	http://eprints.usm.my/60358/1/TEH%20HUI%20WEN%20-%20TESIS%20cut.pdf
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id	my-usm-ep.60358
record_format	uketd_dc
spelling	my-usm-ep.603582024-04-05T07:36:37Z In Silico Screening For The Identification And Characterization Of Potential Mutations That Confer To Antibiotic Resistance In Malaysian Mdr-Tb Isolates 2023-02 Teh, Hui Wen R5-920 Medicine (General) The emergence of multidrug resistance tuberculosis (MDR-TB) is caused by the adaptation of Mycobacterium tuberculosis to survive in the presence of antibiotic, which is also contributed by mutations in the MDR-associated genes. Previous studies showed that the knockdown of fhaA gene expression led to peptidoglycan (PG) precursors the accumulating at the bacillary septum and poles, this indicates a probable defect in PG biosynthesis. As a result, the cell wall becomes impermeable to antibiotic, causing 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 13 samples, in fhaA gene (RV0020c). Subsequent structural analysis shows that the deletion is located at the locus position 243-248, located near the N-terminal of the FHAA protein. Since FHAA protein has a function by binding to MviN protein, it regulates cell growth and peptidoglycan synthesis, we postulated that the deletion will potentially cause the loss of its binding affinity to MviN, resulting in the inhibition and blockage of the peptidoglycan polymerization, causing MDR in MTB. Similarly, another 6 amino acid deletion was also detected for hbhA gene (Rv0475) in 12/14 drug resistant samples. HBHA protein has a function of inducing aggregation in mycobacterial. 2023-02 Thesis http://eprints.usm.my/60358/ http://eprints.usm.my/60358/1/TEH%20HUI%20WEN%20-%20TESIS%20cut.pdf application/pdf en public masters Universiti Sains Malaysia Institut Perubatan & Pergigian Termaju
institution	Universiti Sains Malaysia
collection	USM Institutional Repository
language	English
topic	R5-920 Medicine (General)
spellingShingle	R5-920 Medicine (General) Teh, Hui Wen In Silico Screening For The Identification And Characterization Of Potential Mutations That Confer To Antibiotic Resistance In Malaysian Mdr-Tb Isolates
description	The emergence of multidrug resistance tuberculosis (MDR-TB) is caused by the adaptation of Mycobacterium tuberculosis to survive in the presence of antibiotic, which is also contributed by mutations in the MDR-associated genes. Previous studies showed that the knockdown of fhaA gene expression led to peptidoglycan (PG) precursors the accumulating at the bacillary septum and poles, this indicates a probable defect in PG biosynthesis. As a result, the cell wall becomes impermeable to antibiotic, causing 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 13 samples, in fhaA gene (RV0020c). Subsequent structural analysis shows that the deletion is located at the locus position 243-248, located near the N-terminal of the FHAA protein. Since FHAA protein has a function by binding to MviN protein, it regulates cell growth and peptidoglycan synthesis, we postulated that the deletion will potentially cause the loss of its binding affinity to MviN, resulting in the inhibition and blockage of the peptidoglycan polymerization, causing MDR in MTB. Similarly, another 6 amino acid deletion was also detected for hbhA gene (Rv0475) in 12/14 drug resistant samples. HBHA protein has a function of inducing aggregation in mycobacterial.
format	Thesis
qualification_level	Master's degree
author	Teh, Hui Wen
author_facet	Teh, Hui Wen
author_sort	Teh, Hui Wen
title	In Silico Screening For The Identification And Characterization Of Potential Mutations That Confer To Antibiotic Resistance In Malaysian Mdr-Tb Isolates
title_short	In Silico Screening For The Identification And Characterization Of Potential Mutations That Confer To Antibiotic Resistance In Malaysian Mdr-Tb Isolates
title_full	In Silico Screening For The Identification And Characterization Of Potential Mutations That Confer To Antibiotic Resistance In Malaysian Mdr-Tb Isolates
title_fullStr	In Silico Screening For The Identification And Characterization Of Potential Mutations That Confer To Antibiotic Resistance In Malaysian Mdr-Tb Isolates
title_full_unstemmed	In Silico Screening For The Identification And Characterization Of Potential Mutations That Confer To Antibiotic Resistance In Malaysian Mdr-Tb Isolates
title_sort	in silico screening for the identification and characterization of potential mutations that confer to antibiotic resistance in malaysian mdr-tb isolates
granting_institution	Universiti Sains Malaysia
granting_department	Institut Perubatan & Pergigian Termaju
publishDate	2023
url	http://eprints.usm.my/60358/1/TEH%20HUI%20WEN%20-%20TESIS%20cut.pdf
_version_	1804888920912035840

In Silico Screening For The Identification And Characterization Of Potential Mutations That Confer To Antibiotic Resistance In Malaysian Mdr-Tb Isolates

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