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J Infect Public Health. 2019 Feb 6. pii: S1876-0341(19)30058-9. doi: 10.1016/j.jiph.2019.01.056. [Epub ahead of print]

Mutational analysis of gyrB at amino acids: G481A & D505A in multidrug resistant (MDR) tuberculosis patients.

Author information

1
Department of Biochemistry & Department of Human Genetics and Molecular Biology, University of Health Sciences, Lahore, Pakistan; Department of Cell and Systems Biology, University of Toronto, Canada. Electronic address: nasir.sbs1@outlook.com.
2
Department of Biology, Lahore Garrison University, Lahore, Pakistan.
3
Department of Sciences and Humanities, National University of Computer & Emerging Sciences (NUCES), Foundation for Advancement of Science and Technology (FAST), Lahore, Pakistan.

Abstract

BACKGROUND:

The MDR (multidrug resistance) tuberculosis is a serious public health concern. Fluoroquinolones are in use to treat tuberculosis, but M. tuberculosis strains have now become resistant due to several mutations in different genes. We evaluated mutations in gyrB gene at amino acid positions G481A and D505A of M. tuberculosis by semi-multiplex allele specific (MAS) PCR.

METHODS:

The information on gender, age, type of tuberculosis (TB), positive/negative for MDR-TB and HIV infection was gathered. The genomic DNA isolation from sputum culture samples (n=53) was carried out by non-column based method. The gyrB mutations were investigated by using self-designed primers in semi MAS-PCR, at mentioned amino acid positions.

RESULTS:

There were 38% male patients and 62% were female patients. Most of MDR-TB patients (58.5%) were in the age between 16-30years. There were 90.5% cases of pulmonary TB and 9.4% cases of extra pulmonary TB. Only 1.8% patients were co-infected with HIV. The 24 samples had mutation in gyrB gene out of 53 (45.28%), on both of positions of amino acids Gly481Ala and Asp505Ala. All samples had mutations at Gly481Ala, whereas, 24 samples (45.28%) had mutations at Asp505Ala.

CONCLUSION:

Mutations at amino acids positions 481 and 505 were involved in MDR-TB, which could further develop into an extensively-drug resistance (XDR) TB. Therefore, there is a need to explore all mutations in gyrB gene in MDR-TB, because it can result in a Fluoroquinolones resistance.

KEYWORDS:

Asp505Ala; Gly481Ala; Multi-drug resistance (MDR) TB; Semi-multiplex allele specific (MAS) PCR; gyrB

PMID:
30738756
DOI:
10.1016/j.jiph.2019.01.056
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