Oxidative and nitrosative stress defences of Helicobacter and Campylobacter species that counteract mammalian immunity

Abstract

Helicobacter and Campylobacter species are Gram-negative microaerophilic host-associated heterotrophic bacteria that invade the digestive tract of humans and animals. Campylobacter jejuni is the major worldwide cause of foodborne gastroenteritis in humans, while Helicobacter pylori is ubiquitous in over half of the world's population causing gastric and duodenal ulcers. The colonisation of the gastrointestinal system by Helicobacter and Campylobacter relies on numerous cellular defences to sense the host environment and respond to adverse conditions, including those imposed by the host immunity. An important antimicrobial tool of the mammalian innate immune system is the generation of harmful oxidative and nitrosative stresses to which pathogens are exposed during phagocytosis. This review summarises the regulators, detoxifying enzymes and subversion mechanisms of Helicobacter and Campylobacter that ultimately promote the successful infection of humans.

Keywords: Helicobacter; Campylobacter; pathogen; innate immunity; bacterial defences.

Graphical Abstract Figure.

This review summarises the regulators, detoxifying enzymes and subversion mechanisms of Helicobacter and Campylobacter that ultimately promote the successful infection of humans.

Figure 1.

Biochemical pathways of oxidative and nitrosative species production within host or bacterial cells. Molecular oxygen is reduced to superoxide within innate immune cells by NADPH oxidase or produced inadvertently by complexes of the respiratory electron transport chain. Within neutrophils and inflammatory monocytes, H₂O₂ formed by dismutation of O₂^•− is converted to toxic HOCl by myeloperoxidase. Generation of the powerful oxidising species, the hydroxyl radical, is produced by the Fenton chemistry within the host and/or bacterial cells. Macrophages produce nitric oxide via NO synthase, which can interact with superoxide to produce peroxynitrite. Autoxidation of NO produces N₂O₃ and subsequent downstream reactions generate nitrogen dioxide radicals. The generation of ROS and RNS plays an important role in antibacterial defence by damaging important Campylobacter and Helicobacter cellular molecules.

Figure 2.

Biological targets damaged by ROS and RNS, regulators, direct detoxification defences and indirect protective systems against RNS and ROS in Campylobacter and Helicobacter species. RNS and ROS species damage important biological molecules such as DNA, lipids, haem and Fe-S clusters. Transcriptional and post-transcriptional regulators important for ROS/RNS defence are shown. Fur, AcnB and CrsA are present in H. pylori and C. jejuni; ArsRS, HsrA, CrsRS and Hp110 are expressed in H. pylori and regulators indicated in the right column are active in C. jejuni. Detoxification and repair enzymes of H. pylori (white), C. jejuni (blue) and common to both pathogens (white-blue gradient) that protect against oxidative and nitrosative stress are indicated in black and blue, respectively. ETC, respiratory electron transfer chain.