A balancing act: efflux/influx in mycobacterial drug resistance.
Gail E. Louw,Robin M. Warren,N. C. Gey van Pittius,Christopher R.E. McEvoy,P. D. van Helden,Tommie C. Victor +5 more
TLDR
The tubercle bacillus has become a central player in the epidemiology of diarrheal disease and its role in this disease has become increasingly important in the management of infectious disease outbreaks.Abstract:
Since the discovery of the tubercle bacillus by Robert Koch in 1882 ([110][1]), a greater understanding of the dynamics and survival mechanisms of this pathogen has led to more questions than answers. Despite stringent control strategies and many advances in our knowledge of the epidemiology ofread more
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Journal ArticleDOI
Efflux-mediated drug resistance in bacteria: an update.
Xian-Zhi Li,Hiroshi Nikaido +1 more
TL;DR: The multifaceted implications of drug efflux transporters warrant novel strategies to combat multidrug resistance in bacteria.
Journal ArticleDOI
Mycobacterium abscessus: a new antibiotic nightmare
TL;DR: A review of previous and recent findings on the resistance of M. abscessus to antibiotics highlights the work needed to decipher the molecular events responsible for its extensive chemotherapeutic resistance and raises the profile of this important pathogen.
Journal ArticleDOI
Routine Use of Microbial Whole Genome Sequencing in Diagnostic and Public Health Microbiology
Claudio U. Köser,Matthew J. Ellington,Edward J. P. Cartwright,Edward J. P. Cartwright,Stephen H. Gillespie,Nicholas M. Brown,Mark Farrington,Matthew T. G. Holden,Gordon Dougan,Stephen D. Bentley,Julian Parkhill,Sharon J. Peacock +11 more
TL;DR: It is proposed that molecular epidemiology performed for surveillance and outbreak investigation and genotypic antimicrobial susceptibility testing for microbes that are difficult to grow represent the most immediate areas for application of WGS.
Journal ArticleDOI
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.
Genomic analysis identifies targets of convergent positive selection in drug-resistant Mycobacterium tuberculosis
Maha R. Farhat,B. Jesse Shapiro,Karen J. Kieser,Razvan Sultana,Karen R. Jacobson,Karen R. Jacobson,Thomas C. Victor,Robin M. Warren,Elizabeth M. Streicher,Alistair Calver,Alexander Sloutsky,Devinder Kaur,Jamie E. Posey,Bonnie B. Plikaytis,Marco R. Oggioni,Jennifer L. Gardy,James C. Johnston,Mabel Rodrigues,Patrick Tang,Midori Kato-Maeda,Mark L. Borowsky,Bhavana Muddukrishna,Barry N. Kreiswirth,Natalia Kurepina,James E. Galagan,Sebastien Gagneux,Sebastien Gagneux,Bruce W. Birren,Eric J. Rubin,Eric S. Lander,Pardis C. Sabeti,Megan Murray +31 more
TL;DR: In this article, the authors identified genome-wide signatures of positive selection specific to the 47 drug-resistant strains of M. tuberculosis and identified positive selection in 39 genomic regions in resistant isolates, encoding components in cell wall biosynthesis, transcriptional regulation and DNA repair pathways.
References
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Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence
Stewart T. Cole,Roland Brosch,Julian Parkhill,Thierry Garnier,Carol Churcher,David Harris,Stephen V. Gordon,Karin Eiglmeier,S. Gas,Clifton E. Barry,Fredj Tekaia,K. Badcock,D. Basham,D. Brown,Tracey Chillingworth,R. Connor,Robert L. Davies,K. Devlin,Theresa Feltwell,S. Gentles,N. Hamlin,S. Holroyd,T. Hornsby,Kay Jagels,Anders Krogh,J. McLean,Sharon Moule,Lee Murphy,K. Oliver,J. Osborne,Michael A. Quail,Marie-Adèle Rajandream,Jane Rogers,S. Rutter,K. Seeger,Jason Skelton,Rob Squares,S. Squares,John Sulston,K. Taylor,Sally Whitehead,Bart Barrell +41 more
TL;DR: The complete genome sequence of the best-characterized strain of Mycobacterium tuberculosis, H37Rv, has been determined and analysed in order to improve the understanding of the biology of this slow-growing pathogen and to help the conception of new prophylactic and therapeutic interventions.
Journal ArticleDOI
Distantly related sequences in the alpha- and beta-subunits of ATP synthase, myosin, kinases and other ATP-requiring enzymes and a common nucleotide binding fold.
TL;DR: Related sequences in both alpha and beta and in other enzymes that bind ATP or ADP in catalysis help to identify regions contributing to an adenine nucleotide binding fold in both ATP synthase subunits.
Journal ArticleDOI
The Envelope of Mycobacteria
TL;DR: Differences in mycolic acid structure may affect the fluidity and permeability of the bilayer, and may explain the different sensitivity levels of various mycobacterial species to lipophilic inhibitors.
Journal ArticleDOI
Detection of rifampicin-resistance mutations in Mycobacterium tuberculosis
Amalio Telenti,P Imboden,F Marchesi,Lukas Matter,K Schopfer,Thomas Bodmer,Douglas B. Lowrie,M.J Colston,Stewart T. Cole +8 more
TL;DR: Substitution of a limited number of highly conserved aminoacids encoded by the rpoB gene appears to be the molecular mechanism responsible for "single step" high-level resistance to rifampicin in M tuberculosis, a marker of multidrug-resistant tuberculosis.
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Molecular genetic basis of antimicrobial agent resistance in Mycobacterium tuberculosis: 1998 update.
TL;DR: Although remarkable advances have been made, much remains to be learned about the molecular genetic basis of drug resistance in Mycobacterium tuberculosis, it is reasonable to believe that development of new therapeutics based on knowledge obtained from the study of the molecular mechanisms of resistance will occur.
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