Peptidoglycan synthesis in Tannerella forsythia: scavenging is the modus operandi

Tannerella forsythia is a Gram-negative oral pathogen strongly associated with periodontitis. This bacterium has an absolute requirement for exogenous Nacetylmuramic acid (MurNAc), an amino sugar which forms the repeating disaccharide unit with amino sugar N-acetylglucosamine (GlcNAc) of the peptidoglycan backbone. In silico genome analysis indicates that T. forsythia lacks the key biosynthetic enzymes needed for the de novo synthesis of MurNAc, and thus relies on alternative ways to meet its requirement for peptidoglycan biosynthesis. In the subgingival niche, the bacterium can acquire MurNAc and peptidoglycan fragments (muropeptides) released by the cohabiting bacteria during their cell wall breakdown associated with cell division.T. forsythia is able to also utilize host sialic acid (Neu5Ac) in lieu of MurNAc or muropeptides for its survival during the biofilm growth. The evidence suggests that the bacterium might be able to shunt sialic acid into a metabolic pathway leading to peptidoglycan synthesis. In this review, we explore the mechanisms by which T. forsythia is able to scavenge MurNAc, muropeptide, and sialic acid for its peptidoglycan synthesis, and the impact of these scavenging activities on pathogenesis.