A Comparative Genomics Approach for Shortlisting Broad-Spectrum Drug Targets in Nontuberculous Mycobacteria

Microb Drug Resist. 2021 Feb;27(2):212-226. doi: 10.1089/mdr.2020.0161. Epub 2020 Jun 16.

Abstract

Many members of nontuberculous mycobacteria (NTM) are opportunistic pathogens causing several infections in animals. The incidence of NTM infections and emergence of drug-resistant NTM strains are rising worldwide, emphasizing the need to develop novel anti-NTM drugs. The present study is aimed to identify broad-spectrum drug targets in NTM using a comparative genomics approach. The study identified 537 core proteins in NTM of which 45 were pathogen specific and essential for the survival of pathogens. Furthermore, druggability analysis indicated that 15 were druggable among those 45 proteins. These 15 proteins, which were core proteins, pathogen-specific, essential, and druggable, were considered as potential broad-spectrum candidates. Based on their locations in cytoplasm and membrane, targets were classified as drug and vaccine targets. The identified 15 targets were different enzymes, carrier proteins, transcriptional regulator, two-component system protein, ribosomal, and binding proteins. The identified targets could further be utilized by researchers to design inhibitors for the discovery of antimicrobial agents.

Keywords: broad-spectrum targets; comparative genomics; core proteins; druggability; functional analysis; nontuberculous mycobacteria.

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Genomics / methods
  • Mycobacterium Infections, Nontuberculous / drug therapy*
  • Mycobacterium Infections, Nontuberculous / microbiology
  • Nontuberculous Mycobacteria / drug effects*
  • Nontuberculous Mycobacteria / genetics*

Substances

  • Anti-Bacterial Agents