TY - JOUR
T1 - Increased expression of efflux pump genes in extensively drug-resistant isolates of Mycobacterium tuberculosis
AU - Kanji, Akbar
AU - Hasan, Rumina
AU - Zhang, Ying
AU - Shi, Wanliang
AU - Imtiaz, Kehkashan
AU - Iqbal, Kiran
AU - Shafiq, Samreen
AU - Hasan, Zahra
N1 - Publisher Copyright:
© 2016
PY - 2016/12/1
Y1 - 2016/12/1
N2 - Introduction Extensively drug-resistant tuberculosis (XDR-TB) is defined as tuberculosis (TB) caused by Mycobacterium tuberculosis (MTB) strains that are multidrug resistant (MDR) and also resistant to a fluoroquinolone and to one injectable aminoglycoside or capreomycin. Whilst resistance in MTB has been associated with single nucleotide polymorphisms (SNPs), efflux pumps are thought to play a role in conferring resistance to MTB but little is known about them. Methods We studied XDR MTB (n = 10) strains characterized by whole genome sequencing (WGS; http://www.ebi.ac.uk/ena/data/view/PRJEB7798). Phenotypic susceptibility testing was performed by the MGIT 960 (Becton, Dickinson and Co., NJ, USA) method. All XDR MTB strains were resistant to at least seven drugs whilst one XDR MTB strain, X54 was resistant to isoniazid, rifampicin, pyrazinamide, streptomycin, ethambutol, fluoroquinolones, capreomycin, kanamycin, amikacin, and ethionamide. The mRNA expression of efflux candidate genes Rv0194, Rv2688c, Rv1634, drrA, and drrB was determined in XDR MTB strains as compared with the ATCC reference strain, H37Rv, and drug-susceptible (DS) MTB (n = 9) strains using the relative quantification method normalized to 16S rRNA. Results The mRNA expression levels of efflux genes Rv2688c (p = 0.0037), Rv1634 (p = 0.0042), drrA (p = 0.0078) and drrB (p = 0.0003) were upregulated in XDR-TB strains as compared with DS MTB strains. Conclusion The differences between XDR-TB and drug-susceptible isolates suggest that the increased expression levels of MTB efflux pump genes may contribute to drug resistance in extensively drug-resistant tuberculosis. Future studies are needed to determine whether combining efflux pump inhibitors to antitubercular drugs would be effective to treat resistant tuberculosis.
AB - Introduction Extensively drug-resistant tuberculosis (XDR-TB) is defined as tuberculosis (TB) caused by Mycobacterium tuberculosis (MTB) strains that are multidrug resistant (MDR) and also resistant to a fluoroquinolone and to one injectable aminoglycoside or capreomycin. Whilst resistance in MTB has been associated with single nucleotide polymorphisms (SNPs), efflux pumps are thought to play a role in conferring resistance to MTB but little is known about them. Methods We studied XDR MTB (n = 10) strains characterized by whole genome sequencing (WGS; http://www.ebi.ac.uk/ena/data/view/PRJEB7798). Phenotypic susceptibility testing was performed by the MGIT 960 (Becton, Dickinson and Co., NJ, USA) method. All XDR MTB strains were resistant to at least seven drugs whilst one XDR MTB strain, X54 was resistant to isoniazid, rifampicin, pyrazinamide, streptomycin, ethambutol, fluoroquinolones, capreomycin, kanamycin, amikacin, and ethionamide. The mRNA expression of efflux candidate genes Rv0194, Rv2688c, Rv1634, drrA, and drrB was determined in XDR MTB strains as compared with the ATCC reference strain, H37Rv, and drug-susceptible (DS) MTB (n = 9) strains using the relative quantification method normalized to 16S rRNA. Results The mRNA expression levels of efflux genes Rv2688c (p = 0.0037), Rv1634 (p = 0.0042), drrA (p = 0.0078) and drrB (p = 0.0003) were upregulated in XDR-TB strains as compared with DS MTB strains. Conclusion The differences between XDR-TB and drug-susceptible isolates suggest that the increased expression levels of MTB efflux pump genes may contribute to drug resistance in extensively drug-resistant tuberculosis. Future studies are needed to determine whether combining efflux pump inhibitors to antitubercular drugs would be effective to treat resistant tuberculosis.
UR - http://www.scopus.com/inward/record.url?scp=85048412536&partnerID=8YFLogxK
U2 - 10.1016/j.ijmyco.2016.09.067
DO - 10.1016/j.ijmyco.2016.09.067
M3 - Article
AN - SCOPUS:85048412536
SN - 2212-5531
VL - 5
SP - S150
JO - International Journal of Mycobacteriology
JF - International Journal of Mycobacteriology
ER -
