Combatting bacterial infections by killing persister cells with mitomycin C

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Brian W Kwan1, Nityananda Chowdhury1, Thomas K Wood1,2

  • 1Department of Chemical Engineering, Pennsylvania State University, University Park, PA, 16802-4400, USA.

Environmental Microbiology
|April 11, 2015
PubMed

Insights

The anti-cancer drug mitomycin C (MMC) effectively eradicates dormant bacterial persister cells, which are tolerant to traditional antibiotics. This broad-spectrum compound shows promise for treating chronic infections like cystic fibrosis and tuberculosis.

Area of Science:

  • Microbiology
  • Pharmacology
  • Infectious Diseases

Background:

  • Persister cells are dormant, multi-drug tolerant bacteria contributing to chronic infections.
  • Traditional antibiotics are ineffective against these metabolically inactive persisters.

Purpose of the Study:

  • To investigate the efficacy of the anti-cancer drug mitomycin C (MMC) against bacterial persister cells.
  • To determine if MMC eradicates persisters via a growth-independent mechanism.

Main Methods:

  • Testing MMC's effect on persister cells in various growth states (planktonic, biofilm) and media.
  • Assessing MMC's bactericidal activity against diverse bacterial species (E. coli, S. aureus, P. aeruginosa).
  • Evaluating MMC's efficacy in preclinical animal and wound infection models.

Main Results:

  • Mitomycin C eradicates persister cells through a growth-independent mechanism involving DNA cross-linking.
  • MMC is effective against persisters in planktonic and biofilm cultures across different media.
  • The drug demonstrates broad-spectrum bactericidal activity against multiple pathogenic and commensal bacterial persisters.
  • Successful efficacy was shown in both animal and wound infection models.

Conclusions:

  • Mitomycin C is the first broad-spectrum compound identified to eliminate bacterial persister cells.
  • MMC warrants investigation as a novel therapeutic strategy for recalcitrant bacterial infections.
  • Its growth-independent mechanism offers a new approach to combat antibiotic tolerance.

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