Drug Resistance in Nontuberculous Mycobacteria: Mechanisms and Models

SIMPLE SUMMARY: Recently, there has been a considerable rise in infections caused by nontuberculous mycobacteria (NTM). These mycobacteria, which comprise a large and diverse range of species, have developed resistance to most conventional antibiotics, rendering their treatments unsatisfactory. This review summarizes the mechanisms and strategies adopted by NTMs to evade the action of antimicrobial drugs and techniques that can be used to develop better therapies against them. We also suggest some ways to accelerate the drug development pipeline by utilizing a combination of computational, laboratory and animal testing methods. ABSTRACT: The genus Mycobacteria comprises a multitude of species known to cause serious disease in humans, including Mycobacterium tuberculosis and M. leprae, the responsible agents for tuberculosis and leprosy, respectively. In addition, there is a worldwide spike in the number of infections caused by a mixed group of species such as the M. avium, M. abscessus and M. ulcerans complexes, collectively called nontuberculous mycobacteria (NTMs). The situation is forecasted to worsen because, like tuberculosis, NTMs either naturally possess or are developing high resistance against conventional antibiotics. It is, therefore, important to implement and develop models that allow us to effectively examine the fundamental questions of NTM virulence, as well as to apply them for the discovery of new and improved therapies. This literature review will focus on the known molecular mechanisms behind drug resistance in NTM and the current models that may be used to test new effective antimicrobial therapies.