The Polysaccharide Capsule of Campylobacter jejuni Modulates the Host Immune Response

Maue, Alexander C.; Mohawk, Krystle L.; Giles, David K.; Poly, Frédéric; Ewing, Cheryl P.; Jiao, Yuening; Lee, Ginyoung; Ma, Zuchao; Monteiro, Mário A.; Hill, Christina; Ferderber, Jason; Porter, Chad K.; Trent, M. Stephen; Guerry, Patricia

doi:10.1128/iai.01008-12

Cited by 72 publications

(90 citation statements)

References 56 publications

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“…Although van Alphen et al (24) reported that the population of their strain of 81-176 had the CJJ1420 gene in an off configuration, they constructed a double mutant mutated in both putative transferase genes and showed that this mutant was sensitive to complement killing, an observation consistent with earlier work with the mpnC mutant (23). When the variable regions of both MeOPN transferases were sequenced from the population of our version of strain 81-176, CJJ1420 was also in an off configuration, while CJJ1435 was on.…”

Section: Resultssupporting

confidence: 69%

“…Capsules are a major factor in resistance to complement-mediated killing and, in the case of C. jejuni 81-176 (HS23/36), decoration of the CPS with MeOPN is essential for complement resistance. Thus, mutants of 81-176 expressing a CPS lacking MeOPN were as sensitive to complement-mediated killing as a mutant lacking CPS (23,24,28). CPS of two serotypes, HS2 and HS23/36, have also been shown to have immunomodulatory effects in vitro (23,27), and the immunomodulatory effects for the 81-176 CPS have been confirmed in vivo in a mouse model (29).…”

mentioning

confidence: 83%

“…Thus, mutants of 81-176 expressing a CPS lacking MeOPN were as sensitive to complement-mediated killing as a mutant lacking CPS (23,24,28). CPS of two serotypes, HS2 and HS23/36, have also been shown to have immunomodulatory effects in vitro (23,27), and the immunomodulatory effects for the 81-176 CPS have been confirmed in vivo in a mouse model (29). MeOPN has also been shown to serve as a phage receptor (19,30).…”

mentioning

confidence: 83%

“…jejuni CPS have been shown to be important for pathogenesis. Nonencapsulated mutants were attenuated in a ferret model of diarrheal disease and were reduced in their ability to colonize chickens, mice, and piglets (21)(22)(23)(24)(25), although there are conflicting reports on the role of MeOPN in pathogenesis of a Galleria mellonella model of disease (26,27) and in the invasion of intestinal epithelial cells in vitro (24,28). Capsules are a major factor in resistance to complement-mediated killing and, in the case of C. jejuni 81-176 (HS23/36), decoration of the CPS with MeOPN is essential for complement resistance.…”

mentioning

confidence: 99%

“…Strain 81-176 contains genes predicted to encode two putative MeOPN transferases, CJJ81176_1420 and CJJ81176_1435 (23), here abbreviated to CJJ1420 and CJJ1435, and MeOPN has been reported on both the 2 position of galactose (MeOPN-2-Gal) and the 6 position of galactose (MeOPN-6-Gal) ( Fig. 1) (31; P. Guerry, J. Yuening, and M. A. Monteiro, U.S. provisional patent application 62/075,399).…”

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confidence: 99%

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Phase-Variable Changes in the Position of O -Methyl Phosphoramidate Modifications on the Polysaccharide Capsule of Campylobacter jejuni Modulate Serum Resistance

et al. 2017

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Campylobacter jejuni polysaccharide capsules (CPS) are characterized by the presence of nonstoichiometric O-methyl phosphoramidate (MeOPN) modifications. The lack of stoichiometry is due to phase variation at homopolymeric tracts within the MeOPN transferase genes. C. jejuni strain 81-176 contains two MeOPN transferase genes and has been shown previously to contain MeOPN modifications at the 2 and 6 positions of the galactose (Gal) moiety in the CPS. We demonstrate here that one of the two MeOPN transferases, encoded by CJJ81176_1435, is bifunctional and is responsible for the addition of MeOPN to both the 2 and the 6 positions of Gal. A new MeOPN at the 4 position of Gal was observed in a mutant lacking the CJJ81176_1435 transferase and this was encoded by the CJJ81176_1420 transferase. During routine growth of 81-176, the CJJ81176_1420 transferase was predominantly in an off configuration, while the CJJ81176_1435 transferase was primarily on. However, exposure to normal human serum selected for cells expressing the CJJ81176_1420 transferase. MeOPN modifications appear to block binding of naturally occurring antibodies to the 81-176 CPS. The absence of MeOPN-4-Gal resulted in enhanced sensitivity to serum killing, whereas the loss of MeOPN-2-Gal and MeOPN-6-Gal resulted in enhanced resistance to serum killing, perhaps by allowing more MeOPN to be put onto the 4 position of Gal.IMPORTANCE Campylobacter jejuni undergoes phase variation in genes encoding surface antigens, leading to the concept that a strain of this organism consists of multiple genotypes that are selected for fitness in various environments. Methyl phosphoramidate modifications on the capsule of C. jejuni block access of preexisting antibodies in normal human sera to the polysaccharide chain, thus preventing activation of the classical arm of the complement cascade. We show that the capsule of strain 81-176 contains more sites of MeOPN modifications than previously recognized and that one site, on the 4 position of galactose, is more critical to complement resistance than the others. Exposure to normal human serum selects for variants in the population expressing this MeOPN modification.

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Section: Resultssupporting

confidence: 69%

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confidence: 83%

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confidence: 83%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Phase-Variable Changes in the Position of O -Methyl Phosphoramidate Modifications on the Polysaccharide Capsule of Campylobacter jejuni Modulate Serum Resistance

et al. 2017

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Campylobacter jejuni: Molecular Mechanisms and Animal Models of Colonization and Disease

Gourley

Konkel

2015

Human Emerging and Re‐emerging Infections

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

Myles,

Barnawi,

Mahmoudpour

et al. 2024

MicrobiologyOpen

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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.

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The Polysaccharide Capsule of Campylobacter jejuni Modulates the Host Immune Response

Cited by 72 publications

References 56 publications

Phase-Variable Changes in the Position of O -Methyl Phosphoramidate Modifications on the Polysaccharide Capsule of Campylobacter jejuni Modulate Serum Resistance

Phase-Variable Changes in the Position of O -Methyl Phosphoramidate Modifications on the Polysaccharide Capsule of Campylobacter jejuni Modulate Serum Resistance

Campylobacter jejuni: Molecular Mechanisms and Animal Models of Colonization and Disease

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

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