Author:
Alvarez Luis A.,Kovačič Lidija,Rodríguez Javier,Gosemann Jan-Hendrik,Kubica Malgorzata,Pircalabioru Gratiela G.,Friedmacher Florian,Cean Ada,Ghişe Alina,Sărăndan Mihai B.,Puri Prem,Daff Simon,Plettner Erika,von Kriegsheim Alex,Bourke Billy,Knaus Ulla G.
Abstract
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.
Funder
Science Foundation Ireland
Publisher
Proceedings of the National Academy of Sciences
Cited by
35 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献