A peculiar case of Campylobacter jejuni attenuated aspartate chemosensory mutant, able to cause pathology and inflammation in avian and murine model animals

Abstract

An attenuated Campylobacter jejuni aspartate chemoreceptor ccaA mutant caused gross pathological changes despite reduced colonisation ability in animal models. In chickens, the pathological changes included connective tissue and thickening of the mesenteric fat, as well as the disintegration of the villus tips in the large intestine, whereas in mice, hepatomegaly occurred between 48–72 hours post infection and persisted for the six days of the time course. In addition, there was a significant change in the levels of IL-12p70 in mice infected with the C. jejuni ccaA mutant. CcaA isogenic mutant was hyper-invasive in cell culture and microscopic examination revealed that it had a “run” bias in its “run-and-tumble” chemotactic behaviour. The mutant cells also exhibited lower level of binding to fucosylated and higher binding to sialylated glycan structures in glycan array analysis. This study highlights the importance of investigating phenotypic changes in C. jejuni, as we have shown that specific mutants can cause pathological changes in the host, despite reduction in colonisation potential.

Chemoperception of Specific Amino Acids Controls Phytopathogenicity in Pseudomonas syringae pv. tomato

“…Both proteins were found to bind aspartate with high preference, and the obtained dissociation constants are very similar to those obtained in this study for PsPto-PscA (71–73). Tlp1 (renamed CcaA) of the human pathogen Campylobacter pylori is an aspartate-specific chemoreceptor (46, 74) and was found to play an important role in virulence since experimentation with the mutant strain in different hosts resulted in a number of pathological changes in infection experiments (75). Although the corresponding molecular mechanisms remain unclear, these data underline the importance of signaling mediated by aspartate-specific chemoreceptors.…”

Human campylobacteriosis: A public health concern of global importance

“…C. jejuni infections can occur via various routes such as through direct contact with companion and farm animals or through waterborne or foodborne transmission (Domingues et al., 2012). C. jejuni is a commensal bacterial of chickens which inhabit the chicken intestines at a level >106–108 CFU/g of chicken faeces (Oh et al., 2018) and chickens are the main vector for human campylobacteriosis (Hartley-Tassell et al., 2018). C. jejuni consist of two subspecies; C. jejuni subsp.…”

The dCache Domain of the Chemoreceptor Tlp1 in Campylobacter jejuni Binds and Triggers Chemotaxis toward Formate

“…Previous studies have indicated that the tlp1 gene is strongly upregulated in C. jejuni strains that are colonized in chickens ( 27 ). It may also be involved in the ability of C. jejuni to attach to human intestinal cells in culture ( 28 , 29 ). The tlp1 -isogenic knockout strains had significantly reduced abilities to colonize avian and mammalian hosts, as demonstrated using chicken and mouse models ( 24 , 28 ).…”

“…It may also be involved in the ability of C. jejuni to attach to human intestinal cells in culture ( 28 , 29 ). The tlp1 -isogenic knockout strains had significantly reduced abilities to colonize avian and mammalian hosts, as demonstrated using chicken and mouse models ( 24 , 28 ). However, as the natural ligand of Tlp1 is still unknown, the link between chemotaxis via Tlp1 and physiological functions has not been demonstrated until now.…”