Estimation of efflux mediated multi-drug resistance and its correlation with expression levels of two major efflux pumps in mycobacteria.
Multidrug resistance has been posing an increasing problem in the treatment of tuberculosis. Mutations in the genomic targets of drugs have been identified as the major mechanism behind this resistance. However, high degree of resistance in some isolates towards major drugs like rifampicin, isoniazid, ethambutol and streptomycin can not be explained solely on the basis of mutations. Besides this, certain other mechanisms like efflux pumps have also been considered as alternative mechanisms in the drug resistant isolates where there is no mutation and these mechanisms are specially important for drug resistance in non-tuberculous mycobacteria (NTM). In this study, we have estimated efflux pump mediated drug resistance in different mycobacterial species with the help of efflux pump inhibitors. All major anti-tuberculous drugs have been shown to be extruded by efflux pumps and the degree to which these drugs are extruded, vary in different mycobacterial species and isolates. The correlation of this resistance with functional activity of two major efflux pump genes pstB and Rv1258c was also assessed by reverse transcription PCR. Besides the significant role of these pumps observed, other efflux pumps, present in mycobacteria, may also be involved in drug resistance and need to be investigated.
Gupta
Anuj K
AK
National JALMA Institute for Leprosy and Other Mycobacterial Diseases (ICMR), Agra- 282001, India.
Chauhan
D S
DS
Srivastava
K
K
Das
R
R
Batra
Shweta
S
Mittal
Mayank
M
Goswami
Pooja
P
Singhal
Neelja
N
Sharma
V D
VD
Venkatesan
K
K
Hasnain
S E
SE
Katoch
V M
VM
D018528:ATP-Binding Cassette Transporters / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D006801:Humans; D008826:Microbial Sensitivity Tests; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D009168:Mycobacterium phlei / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics; D009170:Nontuberculous Mycobacteria / Q000187:drug effects* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018088:Tuberculosis, Multidrug-Resistant / Q000235:genetics / Q000378:metabolism*
D018528:ATP-Binding Cassette Transporters; D000251:Adenosine Triphosphatases; D001426:Bacterial Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C519050:Rv1258c protein, Mycobacterium tuberculosis; C120060:phosphate import ATP-binding protein, Bacteria