Journal ArticleDOI
Microarray analysis of efflux pump genes in multidrug-resistant Mycobacterium tuberculosis during stress induced by common anti-tuberculous drugs.
Anuj Kumar Gupta,Vishwa Mohan Katoch,Devendra Singh Chauhan,Rahul Sharma,Mradula Singh,Krishnamurthy Venkatesan,V. D. Sharma +6 more
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TLDR
It was observed that a simultaneous overexpression of efflux pump genes Rv2459, Rv3728, and Rv3065 was associated with resistance to the combination of isoniazid and ethambutol, and these drugs, along with streptomycin, were identified to group together, where efflux-mediated drug resistance appears to be important in M. tuberculosis.Abstract:
Treatment of multidrug-resistant tuberculosis has become one of the major problems in public health. Understanding the molecular mechanisms of drug resistance has been central to tuberculosis research in recent times. DNA microarray technology provides the platform to study the genomic variations related to these mechanisms on a comprehensive level. To investigate the role of efflux pumps in drug resistance, we have constructed a custom DNA microarray containing 25 drug efflux pump genes of Mycobacterium tuberculosis (Indian Patent file no. 2071/DEL/2007) and monitored changes in the expression of these genes on exposure of common anti-tuberculous drugs. Expression profiling of efflux pump genes in multidrug-resistant M. tuberculosis isolates showed overexpression of 10 genes following exposure to various anti-tuberculous drugs. Although two of these genes (Rv3065 and Rv2938) have already been reported to be active drug efflux pumps in M. tuberculosis in earlier studies, the increased activities of other ...read more
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Drug tolerance in replicating mycobacteria mediated by a macrophage-induced efflux mechanism.
Kristin N. Adams,Kevin K. Takaki,Lynn E. Connolly,Heather Wiedenhoft,Kathryn Winglee,Olivier Humbert,Paul H. Edelstein,Christine L. Cosma,Lalita Ramakrishnan +8 more
TL;DR: The existence of multidrug-tolerant organisms that arise within days of infection, are enriched in the replicating intracellular population, and are amplified and disseminated by the tuberculous granuloma are described.
Journal ArticleDOI
Antimicrobial resistance in Mycobacterium tuberculosis: mechanistic and evolutionary perspectives
Sebastian M. Gygli,Sebastian M. Gygli,Sonia Borrell,Sonia Borrell,Andrej Trauner,Andrej Trauner,Sebastien Gagneux,Sebastien Gagneux +7 more
TL;DR: Although the genetic diversity of M. tuberculosis is low compared to other pathogenic bacteria, the strain genetic background has been demonstrated to influence multiple aspects in the evolution of drug resistance.
Journal ArticleDOI
Resistance to Isoniazid and Ethionamide in Mycobacterium tuberculosis: Genes, Mutations, and Causalities
TL;DR: Each known mechanism of resistance to INH and ETH is described and its importance in M. tuberculosis clinical isolates is described.
Journal ArticleDOI
Contribution of Efflux to the Emergence of Isoniazid and Multidrug Resistance in Mycobacterium tuberculosis
Diana Machado,Isabel Couto,João Perdigão,Liliana Rodrigues,Isabel Portugal,Pedro V. Baptista,Bruno Veigas,Leonard Amaral,Miguel Viveiros +8 more
TL;DR: Results support the hypothesis that activity of efflux pumps allows the maintenance of an isoniazid resistant population in a sub-optimally treated patient and should be considered in the development of new therapeutic strategies for preventing the emergence of MDR-TB during treatment.
Journal ArticleDOI
Efflux as a mechanism for drug resistance in Mycobacterium tuberculosis.
Pedro Eduardo Almeida da Silva,Andrea von Groll,Andrea von Groll,Anandi Martin,Juan Carlos Palomino +4 more
TL;DR: The current knowledge on drug efflux in M. tuberculosis is described, which shows Mycobacterium tuberculosis presents one of the largest numbers of putativeDrug efflux pumps compared with its genome size andBioinformatics as well as direct and indirect evidence have established relationships among drug Efflux with intrinsic or acquired resistance in M tuberculosis.
References
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Analysis of relative gene expression data using real-time quantitative pcr and the 2(-delta delta c(t)) method
TL;DR: The 2-Delta Delta C(T) method as mentioned in this paper was proposed to analyze the relative changes in gene expression from real-time quantitative PCR experiments, and it has been shown to be useful in the analysis of realtime, quantitative PCR data.
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Milton H. Saier,Beatty Jt,André Goffeau,Kevin T. Harley,Wilbert H.M. Heijne,Huang Sc,Donald L. Jack,Jähn Ps,Lew K,Jun Liu,Stephanie S. Pao,Ian T. Paulsen,Tsai-Tien Tseng,Virk Ps +13 more
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Journal ArticleDOI
Major Facilitator Superfamily
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Journal ArticleDOI
Massive gene decay in the leprosy bacillus
Stewart T. Cole,Karin Eiglmeier,Julian Parkhill,Keith D. James,Nicholas R. Thomson,Paul R. Wheeler,Nadine Honoré,Thierry Garnier,Carol Churcher,David Harris,Karen Mungall,D. Basham,D. Brown,Tracey Chillingworth,R. Connor,Robert L. Davies,K. Devlin,Stephanie Duthoy,Theresa Feltwell,Audrey Fraser,N. Hamlin,S. Holroyd,T. Hornsby,Kay Jagels,Céline Lacroix,J. Maclean,Sharon Moule,Lee Murphy,K. Oliver,Michael A. Quail,Marie-Adèle Rajandream,Kim Rutherford,S. Rutter,K. Seeger,Sylvie Simon,Mark Simmonds,Jason Skelton,Rob Squares,S. Squares,K. Stevens,K. Taylor,Sally Whitehead,J. R. Woodward,Bart Barrell +43 more
TL;DR: Comparing the 3.27-megabase genome sequence of an armadillo-derived Indian isolate of the leprosy bacillus with that of Mycobacterium tuberculosis provides clear explanations for these properties and reveals an extreme case of reductive evolution.