Mucosal Reactive Oxygen Species Decrease Virulence by Disrupting Campylobacter jejuni Phosphotyrosine Signaling

Nicolae Corcionivoschi, et al. 2012. Cell Host & Microbe 12, 47–59

Speaker: Kuan Chih Wu (武冠志)                                        Time: 15:00~16:00, Oct. 3, 2012

Commentator: Dr. I Hsiu Huang (黃一修 博士)         Place: Room 601

Abstract:

Campylobacter jejuni is a species of Gram-negative, helical-shaped bacilli. C. jejuni infection can cause severe diarrhea and gastroenteritis, and accounting for more than 20% of all deaths under the age of 5 years old children worldwide¹. C. jejuni infection is known to be associated with a variety of serious sequelae, including Guillain-Barre syndrome (GBS), reactive arthritis, and irritable bowel syndrome². Reactive oxygen species (ROS) play an important role in phagocytic and mucosal immunity against bacterial infection³, but how they are induced and interact with bacteria to control the infection is still unclear. In this study, by using in vitro and ex vivo models the authors demonstrated that C. jejuni infection induced ROS release from epithelial cells, and bacterial adhesion and invasion into host cell is needed for ROS induction. Next, the authors showed that hydrogen peroxide exposure impaired the formation of extracellular C. jejuni capsule, an important virulence factor. Previous studies have discovered that ROS modulate tyrosine phosphorylation; some other studies discovered bacterial tyrosine kinase (BY kinase) in bacteria, and this type of kinase is involved in capsular polysaccharide synthesis⁴. Based on these, the authors further designed experiments to investigate the mechanism of capsule down regulation by hydrogen peroxide. They found that ROS inhibited the phosphorylation on tyrosine residues of C. jejuni outer-membrane protein OMP50, a tyrosine kinase, which lead to inactivation of UDP-GlcNAc/Glc 4-epimerase (Gne), an enzyme involve in polysaccharide synthesis, and finally impaired the capsule synthesis.

References:

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4.      Bechet, et al. 2009. Tyrosine-kinases in bacteria: from a matter of controversy to the status of key regulatory enzymes. Amino Acids 37, 499–507.