Phenotypic resistance in mycobacteria: is it because I am old or fat that I resist you?

Robert J H Hammond1, Vincent O Baron2, Katarina Oravcova2

  • 1Medical and Biological Sciences Building, University of St Andrews, North Haugh, St Andrews, Fife KY16 9TF, UK rjhh@st-andrews.ac.uk.

Abstract

Insights

Phenotypic antibiotic resistance in mycobacteria is linked to lipid bodies, not cell age. This finding is crucial for understanding and treating persistent mycobacterial infections.

Area of Science:

  • Microbiology
  • Cell Biology
  • Drug Resistance

Background:

  • Mycobacterial infections often relapse, suggesting underlying mechanisms of persistent or resistant bacteria.
  • Phenotypic resistance, a temporary state not caused by genetic mutation, is a key factor in treatment failure.

Purpose of the Study:

  • To investigate the role of cell age and lipid bodies in the phenotypic resistance of mycobacteria to antibiotics.
  • To determine if lipid-rich cells exhibit differential antibiotic susceptibility compared to lipid-poor cells.

Main Methods:

  • Mycobacterium species (M. smegmatis, M. marinum, M. fortuitum, M. bovis BCG) were cultured.
  • Lipid-rich (LR) and lipid-poor (LP) cells were separated using cell staining and flow cytometry.
  • Minimum bactericidal concentrations (MBCs) were determined for LR and LP cells from young and old cultures.

Main Results:

  • Lipid-rich (LR) cells demonstrated significantly higher antibiotic resistance across all tested mycobacterial species compared to lipid-poor (LP) cells.
  • For Mycobacterium bovis BCG, LR cells showed increased resistance ratios: 5× for rifampicin, 16.7× for isoniazid, 5× for ethambutol, and 5× for ciprofloxacin.
  • This increased phenotypic resistance in LR cells was observed regardless of the age of the bacterial culture.

Conclusions:

  • Phenotypic antibiotic resistance in mycobacteria is directly associated with the presence of intracellular lipid bodies.
  • Cell age does not influence this lipid body-mediated resistance.
  • These findings have significant implications for understanding the persistence of mycobacterial infections and developing strategies to combat relapse.

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