The chemical diversity of the nonulosonic acids of a clinical C. jejuni isolate and a related ∆Cas9 mutant strain

Description

Authors: Jitske van Ede, Chinmoy Saha, Mark van Loosdrecht, Rogier Louwen and Martin Pabst

ABSTRACT
Nonulosonic acids (NulOs) share biosynthetic and structural features across all domains of life, but display an otherwise remarkably large chemical diversity, both in terms of composition and stereochemistry. A distinction can be made between “animal-type” NulOs – commonly referred to as sialic acids – and “bacterial-type” NulOs. The latter are exclusively found in prokaryotes.[1]
In humans, sialic acids are involved in many crucial processes, while in bacteria NulOs are commonly associated with pathogenicity and virulence. Interestingly, the flagellin proteins and lipooligosaccharides (LOS) of Campylobacter jejuni (C. jejuni) – a food borne pathogen that is the leading cause of gastroenteritis worldwide – are extensively modified by a spectrum of NulOs. Both cellular components are also known as important virulence factors. Moreover, sialylated LOS structures on C. jejuni that mimic the human gangliosides may also trigger a serious autoimmune disease called the Guillain-Barré syndrome.[1] [2]
However, the large strain-to-strain heterogeneity and the chemical diversity of nonulosonic acids challenges their analysis, and only little is known about the roles of individual NulO structures. In order to investigate the relevance of the chemical diversity of the nonulosonic acid modifications, we compared the C. jejuni strain GB11 – a clinical isolate that also induces the Guillain-Barré syndrome – with a GB11 ΔCas9 mutant that shows decreased adherence, invasion, intracellular survival, and translocation across human epithelium cells.[3]
In summary, we observed that while the flagella was modified by bacterial-type NulOs, the LOS structures were exclusively sialylated by sialic acids such as NeuAc and NeuAc-OAc. Interestingly, the identified bacterial-type NulOs showed differences in “charge-balancing” and “long-chain” modifications as well as the presence of stereoisomers. These changes are expected to impact the net charge of the flagella and recognition by carbohydrate binding proteins.

Period	7 Sept 2022
Event title	Sialoglyco 2022
Event type	Conference
Location	Nagoya, JapanShow on map
Degree of Recognition	International