Pyrazinamide resistance in Mycobacterium tuberculosis fails to bite?

Alice L den Hertog, Sarah Sengstake, Richard M Anthony

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In contrast to most other antimycobacterial drugs where--particularly in multidrug-resistant (MDR) strains--a limited number of resistance mutations dominate, pyrazinamide (PZA) resistance associated mutations remain highly diverse with limited clustering. This apparent lack of evolutionary selection for successful PZA resistance mechanisms deserves attention. A clear understanding of the epidemiology of PZA resistance acquisition and spread would be expected to result in important insights into how PZA might be better exploited in treatment regimens to minimize the amplification of Mycobacterium tuberculosis (MTB) drug resistance. We propose that PZA resistance typically induces a fitness cost that impairs MTB transmission. This would explain the lack of extensive clustering for PZA-resistant mutants. Our hypothesis also leads to a series of testable predictions which we outline that could confirm or refute our ideas.

Original languageEnglish
JournalFoodborne Pathogens and Disease
Issue number6
Pages (from-to)ftv037
Publication statusPublished - Aug-2015
Externally publishedYes


  • Antitubercular Agents/pharmacology
  • Disease Transmission, Infectious
  • Drug Resistance, Bacterial
  • Humans
  • Mycobacterium tuberculosis/drug effects
  • Pyrazinamide/pharmacology
  • Tuberculosis/microbiology
  • Virulence


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