Sialylation of Porphyromonas gingivalis LPS and its effect on bacterial–host interactions

Abstract

Porphyromonas gingivalis produces different LPS isoforms with significant structural variations of their lipid A and O-antigen moieties that can affect its pro-inflammatory and bone-resorbing potential. We show here, for the first time, that P. gingivalis LPS isolated from W83 strain is highly sialylated and possesses significantly reduced inflammatory potential compared with less sialylated ATCC 33277 strain LPS. Nevertheless, the reduction in the endotoxin activity is not mediated by the presence of sialic acid LPS moieties as the sialic acid-free LPS produced by the mutant W83 strain exhibits a similar inflammatory potential to the wild type strain. Furthermore, our findings suggest that the interaction between the sialic acid LPS moieties and the inhibitory CD33 receptor is prevented by endogenously expressed sialic acid on the surface of THP-1 cells that cannot be out-competed by sialic acid containing P. gingivalis LPS. The present study also highlights the importance of endogenous sialic acid as a ‘self-associated molecular pattern’ and CD33 receptors in modulation of innate immune response as human gingival fibroblasts, which do not express CD33 receptors, and desialylated THP-1 cells have both been found to have much higher spontaneous IL-8 production than naïve THP-1 cells.

N-Glycosylation Alteration of Serum and Salivary Immunoglobulin A Is a Possible Biomarker in Oral Mucositis

“…Although sIgA is more resistant to bacterial proteases than serum IgA [ 3 ], the immunoglobulin-degrading effect of certain periodontal pathogens needs to be considered [ 26 ]. Thus, the highly variable cariological and periodontal status and person-specific oral flora can further affect glycosylation of the secreted sIgA [ 3 , 9 , 27 , 28 , 29 ].…”

Glycan recognition at the saliva – oral microbiome interface

“…Many bacterial genera present in oral biofilms, including Fusobacterium , Neisseria , Porphyromonas, Streptococcus, and Tannerella , express sialic acids or other nonulosonic acids on their surface [194–196]. Bacterial sialic acid may be synthesized de novo , scavenged from host glycans, or produced from host-derived intermediates [197, 198].…”

“…For instance, H. influenzae gains a survival advantage in human serum from presenting sialic acid on lipopolysaccharide (LPS) [199]. Sialylation of Porphyromonas gingivalis LPS appeared to have no effect on its inflammatory potential [196]. The effects of bacterial sialylation may not always be protective when considering the variety of glycan structures underlying the sialic acid and the variety of sialic acid-binding Siglec receptors on eukaryotic cells [200].…”

Interaction between genetic factors, Porphyromonas gingivalis and microglia to promote Alzheimer’s disease

“…CD33 binds to alpha2-3- or alpha2-6-linked sialic acids (N-acetyl neuraminic acid) to which P. gingivalis also binds [ 55 ]. Sialylation of P. gingivalis cell surface components such as LPS may provide additional benefits to this prominent periodontal pathogen in biofilm formation and in escaping complement-mediated killing [ 56 ]. CR1 is highly expressed on CD33+ cells which facilitate P. gingivalis binding to them and is also a general clearance receptor for pathogens [ 57 ].…”