Sequence-Based Predictions of Lipooligosaccharide Diversity in the Neisseriaceae and Their Implication in Pathogenicity

Abstract

Endotoxin [Lipopolysaccharide (LPS)/Lipooligosaccharide (LOS)] is an important virulence determinant in gram negative bacteria. While the genetic basis of endotoxin production and its role in disease in the pathogenic Neisseria has been extensively studied, little research has focused on the genetic basis of LOS biosynthesis in commensal Neisseria. We determined the genomic sequences of a variety of commensal Neisseria strains, and compared these sequences, along with other genomic sequences available from various sequencing centers from commensal and pathogenic strains, to identify genes involved in LOS biosynthesis. This allowed us to make structural predictions as to differences in LOS seen between commensal and pathogenic strains. We determined that all neisserial strains possess a conserved set of genes needed to make a common 3-Deoxy-D-manno-octulosonic acid -heptose core structure. However, significant genomic differences in glycosyl transferase genes support the published literature indicating compositional differences in the terminal oligosaccharides. This was most pronounced in commensal strains that were distally related to the gonococcus and meningococcus. These strains possessed a homolog of heptosyltransferase III, suggesting that they differ from the pathogenic strains by the presence a third heptose. Furthermore, most commensal strains possess homologs of genes needed to synthesize lipopolysaccharide (LPS). N. cinerea, a commensal species that is highly related to the gonococcus has lost the ability to make sialyltransferase. Overall genomic comparisons of various neisserial strains indicate that significant recombination/genetic acquisition/loss has occurred within the genus, and this muddles proper speciation.

Acquisition of the capsule locus by horizontal gene transfer in Neisseria meningitidis is often accompanied by the loss of UDP-GalNAc synthesis

“…Although the role of UDP-Gal and UDP-GalNAc is well described for the pathogenic Neisseria spp., very little is known regarding other species. Immunotyping studies have proposed that N. cinerea, N. polysaccharea and N. lactamica, which possess putative bi-functional galE1 alleles, synthesise a LOS containing Gal and GalNAc residues but no structural studies have been done to confirm this 29 30 31 . The bi-functional meningococcal galE1 alleles ( Supplementary Fig.…”

Metagenomic sequencing reveals microbiota and its functional potential associated with periodontal disease

“…Butyric acid and volatile sulfur compounds cause genomic DNA damage in human gingival epithelial cells. All or part of these virulence factors were discovered in other periodontal bacteria, including A. actinomycetemcomitans 15, P. intermedia 16, T. denticola 17 and Neisseria cinerea 18. However, previous studies have only focused on several toxins of a few well-known pathogens, while virulence factors of other oral bacteria contained in the functional pools have been rarely investigated.…”

Comparison of lipooligosaccharides from human challenge strains of Neisseria gonorrhoeae

“…Studies of the structure of the lipid A and LOS from N. gonorrhoeae (John et al, 1991 ; Yamasaki et al, 1991 , 1994 ; Kerwood et al, 1992 ; Gibson et al, 1993 ) and the genes encoding the gonococcal GTase enzymes (Gotschlich, 1994 ; Erwin et al, 1996 ; Banerjee et al, 1998 ; John et al, 1999 ; Stein et al, 2011 ; Chakraborti et al, 2016 ) have led to a consensus around the prototypical LOS structures as illustrated in Figure 1 . We aimed to use MALDI-TOF MS to profile and compare the structures of the LOS of the human challenge strains MS11 and FA1090.…”