In vitro activity of SPR719 against Mycobacterium ulcerans, Mycobacterium marinum and Mycobacterium chimaera

PLoS Negl Trop Dis. 2021 Jul 26;15(7):e0009636. doi: 10.1371/journal.pntd.0009636. eCollection 2021 Jul.

Abstract

Nontuberculosis mycobacterial (NTM) infections are increasing in prevalence across the world. In many cases, treatment options for these infections are limited. However, there has been progress in recent years in the development of new antimycobacterial drugs. Here, we investigate the in vitro activity of SPR719, a novel aminobenzimidazole antibiotic and the active form of the clinical-stage compound, SPR720, against several isolates of Mycobacterium ulcerans, Mycobacterium marinum and Mycobacterium chimaera. We show that SPR719 is active against these NTM species with a MIC range of 0.125-4 μg/ml and that this compares favorably with the commonly utilized antimycobacterial antibiotics, rifampicin and clarithromycin. Our findings suggest that SPR720 should be further evaluated for the treatment of NTM infections.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • DNA Gyrase / genetics
  • DNA Gyrase / metabolism
  • Drug Resistance, Bacterial
  • Gene Expression Regulation, Bacterial
  • Mutation
  • Mycobacterium / drug effects*
  • Mycobacterium marinum / drug effects*
  • Mycobacterium ulcerans / drug effects*

Substances

  • Anti-Bacterial Agents
  • DNA Gyrase

Supplementary concepts

  • Mycobacterium chimaera

Grants and funding

This work was funded by Spero Therapeutics (sperotherapeutics.com) to SJP and TPS. TL is a current salaried employee of Spero Therapeutics. The funders had no role in study design, data collection and analysis, or decision to publish the manuscript.