4.7 Article

Shooting yourself in the foot: How immune cells induce antibiotic tolerance in microbial pathogens

Journal

PLOS PATHOGENS
Volume 17, Issue 7, Pages -

Publisher

PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.ppat.1009660

Keywords

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Funding

  1. NIAID [R01AI137273, R21159369, R03AI148822]
  2. Burroughs Wellcome Trust Fellowship in the Pathogenesis of Infectious Disease

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Antibiotic treatment failure in the absence of resistance mechanisms is often due to bacteria entering a tolerant state, potentially exacerbated by the actions of phagocytic cells. Understanding the immune-mediated mechanisms of antibiotic tolerance may lead to novel strategies for improving antibiotic therapy.
Antibiotic treatment failure of infection is common and frequently occurs in the absence of genetically encoded antibiotic resistance mechanisms. In such scenarios, the ability of bacteria to enter a phenotypic state that renders them tolerant to the killing activity of multiple antibiotic classes is thought to contribute to antibiotic failure. Phagocytic cells, which specialize in engulfing and destroying invading pathogens, may paradoxically contribute to antibiotic tolerance and treatment failure. Macrophages act as reservoirs for some pathogens and impede penetration of certain classes of antibiotics. In addition, increasing evidence suggests that subpopulations of bacteria can survive inside these cells and are coerced into an antibiotic-tolerant state by host cell activity. Uncovering the mechanisms that drive immune-mediated antibiotic tolerance may present novel strategies to improving antibiotic therapy.

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