Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 113, Issue 37, Pages 10406-10411Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1605443113
Keywords
mucosal immunity; NADPH oxidase; bacterial tyrosine phosphorylation; DOPA; reactive oxygen species (ROS)
Categories
Funding
- National Children Research Centre [K/12/1]
- Science Foundation Ireland [10/IN.1/B2988]
- COST Action [BM1203]
- Science Foundation Ireland (SFI) [10/IN.1/B2988] Funding Source: Science Foundation Ireland (SFI)
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Strengthening the host immune system to fully exploit its potential as antimicrobial defense is vital in countering antibiotic resistance. Chemical compounds released during bidirectional host-pathogen cross-talk, which follows a sensing-response paradigm, can serve as protective mediators. A potent, diffusible messenger is hydrogen peroxide (H2O2), but its consequences on extracellular pathogens are unknown. Here we show that H2O2, released by the host on pathogen contact, subverts the tyrosine signaling network of a number of bacteria accustomed to low-oxygen environments. This defense mechanism uses heme-containing bacterial enzymes with peroxidase-like activity to facilitate phosphotyrosine (p-Tyr) oxidation. An intrabacterial reaction converts p-Tyr to protein-bound dopa (PB-DOPA) via a tyrosinyl radical intermediate, thereby altering antioxidant defense and inactivating enzymes involved in polysaccharide biosynthesis and metabolism. Disruption of bacterial signaling by DOPA modification reveals an infection containment strategy that weakens bacterial fitness and could be a blueprint for antivirulence approaches.
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