Structural diversity inSalmonellaO antigens and its genetic basis

Abstract

This review covers the structures and genetics of the 46 O antigens of Salmonella, a major pathogen of humans and domestic animals. The variation in structures underpins the serological specificity of the 46 recognized serogroups. The O antigen is important for the full function and virulence of many bacteria, and the considerable diversity of O antigens can confer selective advantage. Salmonella O antigens can be divided into two major groups: those which have N-acetylglucosamine (GlcNAc) or N-acetylgalactosamine (GalNAc) and those which have galactose (Gal) as the first sugar in the O unit. In recent years, we have determined 21 chemical structures and sequenced 28 gene clusters for GlcNAc-/GalNAc-initiated O antigens, thus completing the structure and DNA sequence data for the 46 Salmonella O antigens. The structures and gene clusters of the GlcNAc-/GalNAc-initiated O antigens were found to be highly diverse, and 24 of them were found to be identical or closely related to Escherichia coli O antigens. Sequence comparisons indicate that all or most of the shared gene clusters were probably present in the common ancestor, although alternative explanations are also possible. In contrast, the better-known eight Gal-initiated O antigens are closely related both in structures and gene cluster sequences.

Salmonella Serotype Determination Utilizing High-Throughput Genome Sequencing Data

“…However, since O-group prediction from assembled genomes is based on the entire rfb cluster and Salmonella spp. and E. coli share some rfb clusters (26), the presence of an E. coli genome may produce a false-positive Salmonella O-group call (data not shown). The raw sequencing reads approach uses the more discriminatory targets wzx and wzy for O-group identification and is less likely to produce false-positive calls.…”

“…The combined use of the six markers allowed the differentiation of 273 (O3,10) and 72 (O1, 3,19) strains (data not shown). In the two O-group databases, each of the 46 O antigens was represented by a single rfb cluster (26) or a single allele of the wzx or wzy gene (27).…”

Three Wzy polymerases are specific for particular forms of an internal linkage in otherwise identical O units

“…The O units are structurally highly variable in most species, with variation present in the sugars, their order and their linkages. For example there are over 186 O-antigen forms in Escherichia coli (including Shigella) and 46 in Salmonella enterica (Liu et al, 2014;Wang et al, 2010). Most of the genes for synthesis and processing of the O unit are found in a gene cluster, which in S. enterica is between the galF and gnd genes (Liu et al, 2014).…”

“…However despite these differences, the final transferase reaction is to form a glycosidic linkage as in the GT reaction. The two signature proteins of the pathway, Wzx and Wzy, share an interesting characteristic feature, namely the presence of enormous sequence diversity, including in S. enterica (Liu et al, 2014), despite each having a conserved secondary structure and membrane topology (Islam & Lam, 2014). Both are very hydrophobic with multiple trans-membrane segments (TMSs).…”

“…Both of these loops have been shown to be important for Wzy function in the two examples discussed (Islam et al, 2011(Islam et al, , 2013. The diversity of Wzy forms is exemplified by the fact that the 36 Wzy polymerases for N-acetylglucosamine/N-acetylgalactosamine initiated S. enterica O antigens can be divided into 35 distinct homology groups using TribeMCL (Liu et al, 2014), a method that performs rapid and accurate assignment of proteins into families using the Markov cluster algorithm (Enright et al, 2002).…”