Potential impact of efflux pump genes in mediating rifampicin resistance in clinical isolates of Mycobacterium tuberculosis from India

Autor: Kushal Garima, Shraddha Porwal, Archana Bhandekar, Kamal Shrivastava, Anshika Narang, Mridula Bose, Astha Giri, Naresh Kumar Sharma, Mandira Varma-Basil
Rok vydání: 2019
Předmět:
Bacterial Diseases
0301 basic medicine
Extensively Drug-Resistant Tuberculosis
DNA Mutational Analysis
Antitubercular Agents
Gene Expression
Drug resistance
Geographical Locations
Drug Resistance
Multiple
Bacterial
Medicine and Health Sciences
polycyclic compounds
heterocyclic compounds
Multidisciplinary
biology
Actinobacteria
RNA isolation
Infectious Diseases
Hyperexpression Techniques
Medicine
Efflux
Rifampin
Research Article
medicine.drug
DNA
Bacterial
Asia
Tuberculosis
Science
030106 microbiology
India
Microbial Sensitivity Tests
Research and Analysis Methods
Biomolecular isolation
Microbiology
Mycobacterium tuberculosis
03 medical and health sciences
Bacterial Proteins
Genetics
Gene Expression and Vector Techniques
medicine
Humans
Molecular Biology Techniques
Molecular Biology
Molecular Biology Assays and Analysis Techniques
Bacteria
Organisms
Wild type
Biology and Life Sciences
Membrane Transport Proteins
Extensively drug-resistant tuberculosis
biochemical phenomena
metabolism
and nutrition
Tropical Diseases
bacterial infections and mycoses
biology.organism_classification
rpoB
medicine.disease
030104 developmental biology
Mutation
People and Places
bacteria
Rifampicin
Zdroj: PLoS ONE, Vol 14, Iss 9, p e0223163 (2019)
PLoS ONE
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0223163
Popis: Despite the consideration of chromosomal mutations as the major cause of rifampicin (RIF) resistance in M. tuberculosis, the role of other mechanisms such as efflux pumps cannot be ruled out. We evaluated the role of four efflux pumps viz., MmpL2 (Rv0507), MmpL5 (Rv0676c), Rv0194 and Rv1250 in providing RIF resistance in M. tuberculosis. The real time expression of the efflux pumps was analyzed in 16 RIF resistant and 11 RIF susceptible clinical isolates of M. tuberculosis after exposure to RIF. Expression of efflux pumps in these isolates was also correlated with mutations in the rpoB gene and MICs of RIF in the presence and absence of efflux pump inhibitors. Under RIF stress, Rv0194 was induced in 8/16 (50%) RIF resistant and 2/11 (18%) RIF susceptible isolates; mmpL5 in 7/16 (44%) RIF resistant and 1/11 (9%) RIF susceptible isolates; Rv1250 in 4/16 (25%) RIF resistant and 2/11 (18%) RIF susceptible isolates; and mmpL2 was upregulated in 2/16 (12.5%) RIF resistant and 1/11 (9%) RIF susceptible isolates. This preliminary study did not find any association between Rv0194, MmpL2, MmpL5 and Rv1250 and RIF resistance. However, the overexpression of Rv0194 and mmpL5 in greater number of RIF resistant isolates as compared to RIF susceptible isolates and expression of Rv0194 in wild type (WT) resistant isolates suggests a need for further investigations.
Databáze: OpenAIRE
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