NADPH oxidase-derived H2O2 subverts pathogen signaling by oxidative phosphotyrosine conversion to PB-DOPA

Luis A Alvarez, Lidija Kovačič, Javier Rodríguez, Jan-Hendrik Gosemann, Malgorzata Kubica, Gratiela G Pircalabioru, Florian Friedmacher, Ada Cean, Alina Ghişe, Mihai B Sărăndan, Prem Puri, Simon Daff, Erika Plettner, Alex von Kriegsheim, Billy Bourke, Ulla G Knaus

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)10406-10411
Number of pages6
JournalProceedings of the National Academy of Sciences (PNAS)
Issue number37
Early online date25 Aug 2016
Publication statusPublished - 13 Sep 2016


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