Phenotypic and genomic comparison of Mycobacterium aurum and surrogate model species to Mycobacterium tuberculosis: implications for drug discovery

BMC Genomics

Research Article

Amine Namouchi¹  Patricia Charles²  Brigitte Gicquel²  Sandrine Favre-Rochex²  Mena Cimino² 

[1] Centre for Ecological and Evolutionary Synthesis, Department of Biosciences, University of Oslo, P.O. Box 1066, Blindern NO-0316, Oslo, Norway;Unit of Mycobacterial genetics, Institut Pasteur, 25-28, rue du Docteur Roux, 75724, Paris, Cedex 15, France;

关键词: Drug discovery;    Tuberculosis;    Mycobacterium Aurum;    Comparative genomics;    Drug resistance;    Whole genome sequencing;   

DOI  :  10.1186/s12864-017-3924-y

 received in 2017-01-12, accepted in 2017-07-05,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundTuberculosis (TB) is caused by Mycobacterium tuberculosis and represents one of the major challenges facing drug discovery initiatives worldwide. The considerable rise in bacterial drug resistance in recent years has led to the need of new drugs and drug regimens. Model systems are regularly used to speed-up the drug discovery process and circumvent biosafety issues associated with manipulating M. tuberculosis. These include the use of strains such as Mycobacterium smegmatis and Mycobacterium marinum that can be handled in biosafety level 2 facilities, making high-throughput screening feasible. However, each of these model species have their own limitations.ResultsWe report and describe the first complete genome sequence of Mycobacterium aurum ATCC23366, an environmental mycobacterium that can also grow in the gut of humans and animals as part of the microbiota. This species shows a comparable resistance profile to that of M. tuberculosis for several anti-TB drugs. The aims of this study were to (i) determine the drug resistance profile of a recently proposed model species, Mycobacterium aurum, strain ATCC23366, for anti-TB drug discovery as well as Mycobacterium smegmatis and Mycobacterium marinum (ii) sequence and annotate the complete genome sequence of this species obtained using Pacific Bioscience technology (iii) perform comparative genomics analyses of the various surrogate strains with M. tuberculosis (iv) discuss how the choice of the surrogate model used for drug screening can affect the drug discovery process.ConclusionsWe describe the complete genome sequence of M. aurum, a surrogate model for anti-tuberculosis drug discovery. Most of the genes already reported to be associated with drug resistance are shared between all the surrogate strains and M. tuberculosis. We consider that M. aurum might be used in high-throughput screening for tuberculosis drug discovery. We also highly recommend the use of different model species during the drug discovery screening process.

【 授权许可】

CC BY   
© The Author(s). 2017