Characterization of aminoglycoside-resistant genes in mycobacterium tuberculosis clinical strains and role of drug efflux pump genes on kanamycin and amikacin resistance

คุณลักษณะของยีนดื้อยากลุ่มอะมิโนไกลโคไซด์ในเชื้อวัณโรคสายพันธุ์ที่แยกได้ จากผู้ป่วยและบทบาทของยีนขับยาออกนอกเซลล์ต่อการดื้อยากานามัยซินและอะมิกาซิน

Name: Angkanang Sowajassatakul

Name: อังคนางค์ โสวจัสสตากุล

Organization : King Mongkut's Institute of Technology Ladkrabang. Faculty of Science

keyword: Genes

ThaSH: Drug resistance

; Tuberculosis

ThaSH: การดื้อยา

; ยีน

; วัณโรค

Abstract: Tuberculosis (TB) is an infectious respiratory disease caused by an infection of Mycobacterium tuberculosis. The emergency of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) is worldwide public health problem. Therefore, many efforts have focused on studying drug resistance mechanisms and the development of new antituberculosis drugs. In this study, genes associated with aminoglycoside resistance including rrs, eis promoter region, tap, whiB7 and tlyA were investigated in twenty-nine kanamycin-resistant M. tuberculosis clinical strains isolated in Thailand and twenty-seven kanamycin-susceptible strains. This study demonstrated that the majority of kanamycin resistance in Thai M. tuberculosis clinical strains was rrs or 16S rRNA mutation at A1401G. Mutation of rrs at A1401G was found in twenty-one out of twenty-nine kanamycin-resistant strains whereas mutations of eis at C-14T or G-37T were found in the remaining five kanamycin-resistant strains. The other two remaining kanamycin-resistant strains showed lns581C mutation in tap gene. No mutations in all kanamycin resistant genes were found in M. tuberculosis MT433, although it showed a high-level resistance to AMK and KM (64 µg/ml). The expression level of sixteen efflux pump or hypothetical transmembrane genes was investigated by real-time quantitative reverse transcription PCR method (Real-time qRT-PCR). The result revealed that M. tuberculosis MT433 showed a high-level of gene expression in Rv1819c, Rv1877 and Rv2846c (>2.6-fold change) under kanamycin exposure compared to M. tuberculosis MT164 with A1401G rrs mutation. By AMK and KM susceptibility testing in overexpressed M. tuberculosis H37Ra containing Rv1819c, Rv1877 and Rv2846c, these genes was not directly associated with aminoglycoside resistance in M. tuberculosis MT433. However, the high-level expression of eis in this strain might play a role in aminoglycoside resistance

King Mongkut's Institute of Technology Ladkrabang. Central Library

Address: BANGKOK

Email: Lifelong@kmitl.ac.th

Name: |aSaranya Phunpruch

Role: Thesis Advisor

Email : saranya.ph@kmitl.ac.th

Created: 2018

Modified: 2563-05-29

Issued: 2020-05-29

วิทยานิพนธ์/Thesis

application/pdf

CallNumber: EThesis

eng

DegreeName: Doctor of Philosophy (Biotechnology)

Level: Doctoral Degree

Descipline: Biotechnology

©copyrights King Mongkut's Institute of Technology Ladkrabang

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