Effect of common and experimental anti-tuberculosis treatments on Mycobacterium tuberculosis growing as biofilms

PeerJ. 2016 Nov 22:4:e2717. doi: 10.7717/peerj.2717. eCollection 2016.

Abstract

Much is known regarding the antibiotic susceptibility of planktonic cultures of Mycobacterium tuberculosis, the bacterium responsible for the lung disease tuberculosis (TB). As planktonically-grown M. tuberculosis are unlikely to be entirely representative of the bacterium during infection, we set out to determine how effective a range of anti-mycobacterial treatments were against M. tuberculosis growing as a biofilm, a bacterial phenotype known to be more resistant to antibiotic treatment. Light levels from bioluminescently-labelled M. tuberculosis H37Rv (strain BSG001) were used as a surrogate for bacterial viability, and were monitored before and after one week of treatment. After treatment, biofilms were disrupted, washed and inoculated into fresh broth and plated onto solid media to rescue any surviving bacteria. We found that in this phenotypic state M. tuberculosis was resistant to the majority of the compounds tested. Minimum inhibitory concentrations (MICs) increased by 20-fold to greater than 1,000-fold, underlying the potential of this phenotype to cause significant problems during treatment.

Keywords: Ascorbic acid; Biofilm; Fluoroanthranilic acid; MTB; Mycobacterium tuberculosis; Nitroimidazole; Pellicle; TB; Tryptophan biosynthesis.

Grants and funding

This work was supported by the Maurice Wilkins Centre for Molecular Biodiscovery and the University of Auckland Vice-Chancellor’s Strategic Development Fund and Faculty Research Development Fund. SW is supported by a Sir Charles Hercus Fellowship (09/099) from the Health Research Council of New Zealand. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.