Effect of the polysaccharide capsule and its heptose on the resistance of Campylobacter jejuni to innate immune defenses

Abstract

Campylobacter jejuni is a commensal in many animals but causes diarrhea in humans. Its polysaccharide capsule contributes to host colonization and virulence in a strain‐ and model‐specific manner. We investigated if the capsule and its heptose are important for interactions of strain NCTC 11168 with various hosts and their innate immune defenses. We determined that they support bacterial survival in Drosophila melanogaster and enhance virulence in Galleria mellonella. We showed that the capsule had limited antiphagocytic activity in human and chicken macrophages, decreased adherence to chicken macrophages, and decreased intracellular survival in both macrophages. In contrast, the heptose increased uptake by chicken macrophages and supported adherence to human macrophages and survival within them. While the capsule triggered nitric oxide production in chicken macrophages, the heptose mitigated this and protected against nitrosative assault. Finally, the C. jejuni strain NCTC 11168 elicited strong cytokine production in both macrophages but quenched ROS production independently from capsule and heptose, and while the capsule and heptose did not protect against oxidative assault, they favored growth in biofilms under oxidative stress. This study shows that the wild‐type capsule with its heptose is optimized to resist innate defenses in strain NCTC 11168 often via antagonistic effects of the capsule and its heptose.

Campylobacter jejuni virulence factors: update on emerging issues and trends

“…Strain-to-strain variation in the location of heptose sugars within the CPS has also been observed. For example, in strain 81–176, the heptose moiety is an inherent part of the repeating unit of the CPS, whereas strain 11168 possesses a heptose moiety that branches off from the repeating unit [ 79 ]. Because of this, the heptose synthesis mutants of strain 11168 still possess the CPS.…”

“…Because of this, the heptose synthesis mutants of strain 11168 still possess the CPS. Myles et al [ 79 ] have recently taken advantage of this fact by using these mutants to elucidate the distinct roles of the CPS and its branching heptose during infection. The study found that the capsule reduced bacterial adherence to and uptake by chicken macrophages, and decreased intracellular survival, whereas the heptose moieties in the CPS had the opposite effect.…”

“…In addition, the heptose moieties were shown to reduce the capsule-induced nitrogen oxide (NO) generation by chicken macrophages. These findings highlighted the complex interplay of the capsule and its heptose moieties in C. jejuni 11168, suggesting that the CPS structure may undergo evolutionary adaptation to enhance bacterial survival in both commensal and pathogenic contexts [ 79 ].…”