Sialic acid, periodontal pathogens and Tannerella forsythia: stick around and enjoy the feast!

Abstract

Periodontal pathogens, like any other human commensal or pathogenic bacterium, must possess both the ability to acquire the necessary growth factors and the means to adhere to surfaces or reside and survive in their environmental niche. Recent evidence has suggested that sialic acid containing host molecules may provide both of these requirements in vivo for several periodontal pathogens but most notably for the red complex organism Tannerella forsythia. Several other periodontal pathogens also possess sialic acid scavenging enzymes - sialidases, which can also expose adhesive epitopes, but might also act as adhesins in their own right. In addition, recent experimental work coupled with the release of several genome sequences has revealed that periodontal bacteria have a range of sialic acid uptake and utilization systems while others may also use sialic acid as a cloaking device on their surface to mimic host and avoid immune recognition. This review will focus on these systems in a range of periodontal bacteria with a focus on Ta. forsythia.

Figure 1. Sialic acid catabolism and transport clusters from a range of bacteria

Predicted and confirmed sialic acid gene clusters from the genome sequences of the organisms shown are illustrated using standard nan gene descriptors. Key: Catabolic genes: nanA-neuraminate lyase(red), nanE-N-acetylmannosamine-6P epimerase (lime green), nanK-ManNAc kinase (turquoise) ; Inner membrane transporters (yellow) : nanT- Major facilitator Superfamily permease; siaPQM- Neu5Ac TRAP (tripartite ATP-independent periplasmic) transporter; Outer membrane transporter (mid green) : nanOU- TonB dependent sialic acid transport system, nanC-sialic acid specific porin; Accesory genes (Grey) : nanS- sialic acid 9-O-acetylesterase; nahA/hexA-beta hexosaminidase; nanM- sialic acid mutarotase; yhcH- putative Glycolyl sialic acid processing enzyme; estA- sialyl transferase. The first gene in each cluster is noted for each species except the well established E. coli and H. influenzae.

Figure 2. Summary of sialic acid uptake systems present in periodontal bacteria

Sialic acid enters either via either a TonB dependent NanOU type system before entry into the cytoplasm via a NanT MFS permease protein. In organisms that lack a NanOU system it is likely that they employ a NanC type or general porin like OmpC or OmpF that is used in E. coli. This might then feed either to a NanT permease or a SiaPQM TRAP type permease as is the case for H. influenzae.

Figure 3. Model of sialic acid dependent interactions of periodontal pathogens

All of the pathogens shown except for the Fusobacteium spp. Produce cell-anchored or secreted sialidase enzymes (colour coded Pacman for parent strain) that potentially release sialic acid from both bacterial, e.g. LPS of F. polymorphum or arginine gingipain (rgp) of P. gingivalis, and host sources, e.g. cell surface or salivary glycoproteins. The consequences of this removal of sialic acid may also be inter-bacterial interaction or activation of host cell signaling cascades (orange arrows) such as TLR pathways or cytokine release. Key: Ac-acetyl group, ‘s’ in a hexagon- sialic acid residue, Aa- Aggregatibacter actninomyceteconcomitans, rgp- arginine gingipain.