Campylobacter sp.: Pathogenicity factors and prevention methods—new molecular targets for innovative antivirulence drugs?

Abstract

Infections caused by bacterial species from the genus Campylobacter are one of the four main causes of strong diarrheal enteritis worldwide. Campylobacteriosis, a typical food-borne disease, can range from mild symptoms to fatal illness. About 550 million people worldwide suffer from campylobacteriosis and lethality is about 33 million p.a. This review summarizes the state of the current knowledge on Campylobacter with focus on its specific virulence factors. Using this knowledge, multifactorial prevention strategies can be implemented to reduce the prevalence of Campylobacter in the food chain. In particular, antiadhesive strategies with specific adhesion inhibitors seem to be a promising concept for reducing Campylobacter bacterial load in poultry production. Antivirulence compounds against bacterial adhesion to and/or invasion into the host cells can open new fields for innovative antibacterial agents. Influencing chemotaxis, biofilm formation, quorum sensing, secretion systems, or toxins by specific inhibitors can help to reduce virulence of the bacterium. In addition, the unusual glycosylation of the bacterium, being a prerequisite for effective phase variation and adaption to different hosts, is yet an unexplored target for combating Campylobacter sp. Plant extracts are widely used remedies in developing countries to combat infections with Campylobacter. Therefore, the present review summarizes the use of natural products against the bacterium in an attempt to stimulate innovative research concepts on the manifold still open questions behind Campylobacter towards improved treatment and sanitation of animal vectors, treatment of infected patients, and new strategies for prevention. Key points • Campylobacter sp. is a main cause of strong enteritis worldwide. • Main virulence factors: cytolethal distending toxin, adhesion proteins, invasion machinery. • Strong need for development of antivirulence compounds.

Antimicrobial Resistance Profiles, Virulence Genes, and Genetic Diversity of Thermophilic Campylobacter Species Isolated From a Layer Poultry Farm in Korea

“…C. jejuni is known to cause Guillain–Barré syndrome, characterized by acute and progressive neuromuscular paralysis, mediated by sialyltransferases ( cst II) ( Koga et al, 2006 ; Humphrey et al, 2007 ; González-Hein et al, 2013 ). Sialic acid confers immune avoidance to C. jejuni , as a mutant lacking lipooligosaccharide sialic acid residues showed greater immunoreactivity and decreased serum resistance ( Kreling et al, 2020 ). The CDT complex, another important factor in Campylobacter , codes for the cytolethal distending toxin with cdt B acting as the catalytic site, and in the nucleus, cdt B induces cell cycle arrest and leads to apoptosis of both immune and epithelial cells in the intestines ( Jain et al, 2008 ).…”

“…Campylobacter species also possess other genes associated with adhesion ( cad F and pld A), invasion ( cia B), thermo-tolerance ( dna J) ( Pillay et al, 2020 ), and stress response ( csr A) ( Fields and Thompson, 2008 ). Studies have shown that Campylobacter strain mutants for cad F and cia B exhibited a reduced attachment and invasion of INT 407 cell line along with a decline of survival potential ( Kreling et al, 2020 ; Ramires et al, 2020 ).…”

Bacterial Infection and Non-Hodgkin B-Cell Lymphoma: Interactions between Pathogen, Host and the Tumor Environment

“…It can be speculated that, as in the case of H. pylori , CDT-vacuolating cytotoxin enables the destruction of intestinal villi and invasion of the intestinal mucosa. Furthermore, CDT toxin leads to DNA damage as demonstrated in mouse models [ 84 ]. It has been demonstrated that cells exposed to CDT-DNA damaging agents suffer extensive genetic modifications that could cause apoptosis; hence, researchers speculate that the human clinical isolate C. jejuni 81–176 is able to promote colorectal cancer [ 85 ].…”

Bacteriophage Therapy to Reduce Colonization of Campylobacter jejuni in Broiler Chickens before Slaughter

“…Campylobacter is the most commonly reported gastrointestinal bacterial pathogen in humans in the European Union (EU) since 2005, with 220,682 confirmed cases of Campylobacteriosis in 2019 [ 1 ]. Campylobacter spp., in particular Campylobacter jejuni ( C. jejuni ) and Campylobacter coli ( C. coli ), are ubiquitous in nature, and their niche seems to be the intestinal mucosa of warm-blooded hosts [ 2 , 3 ], especially those of avian species. In poultry, the natural bacterial colonization is mainly associated with horizontal transmission at the farm level, and to a lesser extent to vertical transmission [ 4 ], with a mean prevalence in the EU of 71.2% of broiler batches [ 5 ].…”