Structure of the LPS O-chain from Fusobacterium nucleatum strain 10953, containing sialic acid

Abstract

Fusobacterium nucleatum is an anaerobic bacterium found in the human mouth where it causes periodontitis. Recently, it has been gaining attention as a potential causative agent for colorectal cancer and is strongly linked with pregnancy complications including pre-term and still births. Little is known about virulence factors of this organism and thus we have initiated studies to examine the bacterial surface glycochemistry. Consistent with a recent paper suggesting that F. nucleatum strain 10593 can synthesize sialic acid, a staining technique identified sialic acid on the bacterial surface. We isolated lipopolysaccharide from this F. nucleatum strain and performed structural analysis on the O-antigen. Our studies identified a trisaccharide repeating unit of the O-antigen with the following structure: -[→4)-α-Neup5Ac-(2→4)-β-normalD-Galp-(1→3)-α-normalD-FucpNAc4normalNAc-(1-]-where Ac indicates 4-N-acetylation of ∼30% FucNAc4N residues. The presence of sialic acid as a constituent of the O-antigen is consistent with recent data identifying de novo sialic acid synthesis in this strain.

Structure of the O‐Antigen and the Lipid A from the Lipopolysaccharide of Fusobacterium nucleatum ATCC 51191

“…animalis ATCC 51191. Among F. nucleatum strains there is a high variability of O‐antigen structures characterized to date [6,13–19] . According to the Bacterial Carbohydrate Structure Database, [25,27] F. nucleatum ATCC 51191 LPS trisaccharide represents a novel O‐antigen structure for bacterial LPS.…”

Gut microbiota dysbiosis signature is associated with the colorectal carcinogenesis sequence and improves the diagnosis of colorectal lesions

“…LPS comprises four structural domains, which might function in bacterial attachment to the host 38,39 . It has been shown that sialic acid in LPSs can inhibit the immunological response by binding to specific receptors, escape host immune surveillance, and facilitate the formation of biofilms 40 . Interestingly, we found that more than one species was responsible for the observed alteration of microbial function.…”

“…38,39 It has been shown that sialic acid in LPSs can inhibit the immunological response by binding to specific receptors, escape host immune surveillance, and facilitate the formation of biofilms. 40 Interestingly, we found that more than one species was responsible for the observed alteration of microbial function. Taking LPSs as an example, up to six species were found to contribute to the enriched LPS function in CRC.…”

Peptidoglycan synthesis in Tannerella forsythia: Scavenging is the modus operandi

“…We and others have shown that many strains of F. nucleatum express surface sialic acid, 55,56 and specifically in the case of F. nucleatum strains, sialic acid is a component of the lipopolysaccharide O-chain. 55 It is predicted that sialic acid after entering the cell via NanOU/NanT transporter is converted to GlcNAc-6P by the action of NanA, NanK and NanE enzymes encoded by the sialic acid utilization Nan operon 47 (Figure 3). GlcNAc-6P can either enter the energy utilization pathway, or be shunted into a peptidoglycan biosynthetic pathway as depicted in Figure 3.…”

“…Not only epithelial cells, but other bacteria with which T. forsythia is known to interact, such as F. nucleatum can provide sialic acid. We and others have shown that many strains of F. nucleatum express surface sialic acid, and specifically in the case of F. nucleatum strains, sialic acid is a component of the lipopolysaccharide O‐chain . It is predicted that sialic acid after entering the cell via NanOU/NanT transporter is converted to GlcNAc‐6P by the action of NanA, NanK and NanE enzymes encoded by the sialic acid utilization Nan operon (Figure ).…”