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

Abstract

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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-017-3924-y) contains supplementary material, which is available to authorized users.

Fitness Cost and Compensatory Evolution in Levofloxacin-Resistant Mycobacterium aurum

“…Here, we used Mycobacterium aurum as a model organism for studying the fitness cost and compensatory evolution of FQ-R in M. tuberculosis. Compared to other mycobacteria used as models for tuberculosis research, M. aurum does not aggregate, which facilitates precise colony enumeration (11). Although fast growing and nonpathogenic, M. aurum is like M. tuberculosis for FQ-R, and its QRDRs of gyrA and gyrB show amino acid identities of 95 and 97.56%, respectively, with those of M. tuberculosis.…”

Aureolic Acid Group of Agents as Potential Antituberculosis Drugs

“…Considering that Mycobacterium tuberculosis is rather a complex subject (in part, because of its slow growth), the effect of aureolic acid derivatives was tested on its close relative, M. smegmatis [ 11 , 12 ]. It has a similarly high genome GC content, but grows faster and is not pathogenic.…”

A Pharmacological Overview of Alpinumisoflavone, a Natural Prenylated Isoflavonoid

“…Tuberculosis (TB) is the leading human infectious-related cause of death (WHO, 2017). Usually, nonpathogenic mycobacterial species such as Mycobacterium smegmatis are used as model systems (Altaf et al, 2010; Namouchi et al, 2017). M. smegmatis displays an identical susceptibility to that of multidrug-resistant (MDR) clinical isolates of Mycobacterium tuberculosis for the two frontline anti-TB drugs isoniazid and rifampicin (Chaturvedi et al, 2007).…”