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 but also 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 utilisation 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 T. forsythia.

Fusobacterium nucleatum and Tannerella forsythia Induce Synergistic Alveolar Bone Loss in a Mouse Periodontitis Model

“…These synergistic effects have been shown to be mediated via the regulation of posttranscriptional turnover and translation of cytokine mRNA (14,43) as well as the NF-B signaling pathways (9). Moreover, the cytokine responses may possibly be influenced by the action of bacterial sialidases on Toll-like receptors (TLRs) (1, 2); T. forsythia NanH sialidase (32,38) might play a role in this regard. Regarding NF-B activation, NF-B is present in the cytoplasm as an inactive heterodimer of an IB family inhibitor subunit, a 50-kDa DNAbinding subunit (p50), and a 65-kDa transactivation subunit (RelA/p65) (17).…”

“…T. forsythia lacks key enzymes needed for the de novo production of this essential amino sugar needed for peptidoglycan synthesis. Still other nutritional relationships may exist; for example, the genome of F. nucleatum strain 25586 contains a complete sialic acid metabolic system (38) and may utilize free sialic acid released by the action of the T. forsythia NanH sialidase enzyme on salivary or epithelial glycoproteins (32). In addition, NanH may act to expose subterminal galactose residues on human glycoproteins to which F. nucleatum is well known to bind via a galactose-binding lectin (26,33).…”

Sialic Acid Residues Are Essential for Cell Lysis Mediated by Leukotoxin from Aggregatibacter actinomycetemcomitans

“…In erythrocytes, LtxA may thus bind to the negatively charged sialic acid alone without the tighter association with ␣ L ␤ 2 -integrin. Interestingly, recent evidence suggests that periodontal pathogens use sialic acid as a growth factor or as a sole carbon source (63), and targeting sialic acid-expressing cells could possibly provide nutrients for A. actinomycetemcomitans in order to grow and replicate.…”

“…Neutralization of negative surface charge, e.g., through reduction/blockage of sialic acids, may limit many of the clinical consequences of toxin attack and thus constrain LtxA's function as a virulence factor. Hemolysis is assumed to be an important physiological source of iron for A. actinomycetemcomitans, since the bacterium is unable to retrieve iron from human transferrin and lactoferrin (63,64). Iron is an essential nutrient for most bacteria, and the ability to acquire iron is recognized as one of the key steps in the survival of a pathogen in its host (65).…”

Production, purification and crystallization of atrans-sialidase fromTrypanosoma vivax

“…Like the cells of the animal host, pathogens and commensals can decorate their surfaces with SA (Varki & Gagneux, 2012). This helps pathogens to modulate the host's immune system, to avoid immune recognition and to invade host cells (Stafford et al, 2012;Montagna et al, 2006;Schenkman et al, 1991;BlomPotar et al, 2010;Muiá et al, 2010;Schauer & Kamerling, 2011). In addition, some pathogens require host-derived SA for nutritional requirements.…”