Lipopolysaccharide of the Yersinia pseudotuberculosis Complex

Abstract

Lipopolysaccharide (LPS), localized in the outer leaflet of the outer membrane, serves as the major surface component of the Gram-negative bacterial cell envelope responsible for the activation of the host’s innate immune system. Variations of the LPS structure utilized by Gram-negative bacteria promote survival by providing resistance to components of the innate immune system and preventing recognition by TLR4. This review summarizes studies of the biosynthesis of Yersinia pseudotuberculosis complex LPSs, and the roles of their structural components in molecular mechanisms of yersiniae pathogenesis and immunogenesis.

Lipopolysaccharide-Induced Model of Neuroinflammation: Mechanisms of Action, Research Application and Future Directions for Its Use

“…The LPS molecule consists of lipid A, core oligosaccharide and O-polysaccharide also referred to as O-antigen ( Figure 1 ). Hydrophobic lipid A is the most immunogenic part of the LPS, embedded in the bacterial outer membrane and merging it with the rest of the LPS molecule [ 30 ]. Lipid A is the most stable component of LPS, as O-oligosaccharide and core moieties may vary significantly even among the same bacteria species.…”

“…However, even in the conservative lipid A, slight chemical differences can occur like a variability in acylation and phosphorylation levels, which can result in a diverse immunogenicity of LPS. The influence of the lipid A structure on LPS immunogenicity is well-described and currently it is believed that a six-acyl chain (hexa-acylated) lipid A is the most immunogenic form of LPS [ 29 , 30 ], [ 31 ]. This relationship provides a fundamental base for immune distinguish between pathogenic and non-pathogenic bacteria [ 32 ].…”

“…Nevertheless, some bacteria have developed strategies to elude the immune recognition of hexa-acylated lipid A and increase survival in the host’s environment. These mechanisms include modifications of the lipid A by adding 4-amino-arabinose (Ara4N) residues or ethanolamine to phosphate groups, removing phosphate groups, or finally, by shortening or lengthening of acyl chains [ 30 , 34 ]. For example, virulent Gram-negative bacteria Yersinia pestis and Yersinia pseudotuberculosis produce highly immunogenic hexa-acylated lipid A in lower ambient temperatures, but at the temperature of a mammalian body, namely 37 °C, the less active tetra-acylated form is expressed [ 30 ].…”

Pathogenicity and virulence of Yersinia

“…The canonical lipidation structure of gram-negative LPS consists of four to seven fatty acid chains, with the hexa-acylated form more commonly found in enteric bacterial pathogens. All three pathogenic Yersiniae synthesize hypoacylated lipid A at 37℃ compared to the hexa-acylated form at lower temperatures, as do other gram-negative bacteria [ 216 , 217 ]. For Y. enterocolitica and Y. pestis , hypoacylation of lipid A due to the thermal down-regulation of acylation plays an important role in mammalian virulence, likely due to the neutralization of host TLR4-recognition of LPS [ 218–220 ].…”

Phosphoethanolamine Transferases as Drug Discovery Targets for Therapeutic Treatment of Multi-Drug Resistant Pathogenic Gram-Negative Bacteria

“…The eptB gene has also been identified in the genome of Yersinia pestis , which shares a high sequence identity (63%) and has an absolute functional identity to the E. coli eptB [ 87 ]. The incorporation of a PEA moiety on Kdo was detected in the LPS of wild-type Y. pestis grown at very low temperature (6 °C) while in the same cultivation conditions no PEA was revealed in the LPS of the eptB mutant strain [ 88 , 89 ].…”