학술논문
The low level of O antigen in Salmonella enterica Paratyphi A is due to inefficiency of the glycosyltransferase WbaV
RESEARCH LETTER - Pathogens & Pathogenicity
RESEARCH LETTER - Pathogens & Pathogenicity
Document Type
Report
Source
FEMS Microbiology Letters. February 1, 2021, Vol. 368 Issue 3, p1g, 8 p.
Subject
Language
English
ISSN
0378-1097
Abstract
INTRODUCTION Enteric fever is a major disease burden in many developing countries, with the potential for severe and even life-threatening complications (Gibani, Britto and Pollard 2018). Until recently, Salmonella enterica [...]
The group A O antigen is the major surface polysaccharide of Salmonella enterica serovar Paratyphi A (SPA), and the focal point for most current vaccine development efforts. The SPA O-antigen repeat (O unit) is structurally similar to the group D1 O unit of S. enterica serovar Typhi, differing only in the presence of a terminal side-branch paratose (Par) in place of tyvelose (Tyv), both of which are attached by the glycosyltransferase WbaV. The two O-antigen gene clusters are also highly similar, but with a loss-of-function mutation in the group A tyv gene and the tandem amplification of wbaV in most SPA strains. In this study, we show that SPA strains consistently produce less O antigen than their group D1 counterparts and use an artificial group A strain (D1 [DELTA]tyv) to show this is due to inefficient Par attachment by WbaV. We also demonstrate that group A O-antigen production can be increased by overexpression of the wbaV gene in both the D1 [DELTA]tyv strain and two multi-wbaV SPA strains. These findings should be broadly applicable in ongoing vaccine development pipelines, where efficient isolation and purification of large quantities of O antigen is of critical importance. Keywords: Paratyphi A; O antigen, biosynthesis; glycosyltransferase; WbaV; paratose
The group A O antigen is the major surface polysaccharide of Salmonella enterica serovar Paratyphi A (SPA), and the focal point for most current vaccine development efforts. The SPA O-antigen repeat (O unit) is structurally similar to the group D1 O unit of S. enterica serovar Typhi, differing only in the presence of a terminal side-branch paratose (Par) in place of tyvelose (Tyv), both of which are attached by the glycosyltransferase WbaV. The two O-antigen gene clusters are also highly similar, but with a loss-of-function mutation in the group A tyv gene and the tandem amplification of wbaV in most SPA strains. In this study, we show that SPA strains consistently produce less O antigen than their group D1 counterparts and use an artificial group A strain (D1 [DELTA]tyv) to show this is due to inefficient Par attachment by WbaV. We also demonstrate that group A O-antigen production can be increased by overexpression of the wbaV gene in both the D1 [DELTA]tyv strain and two multi-wbaV SPA strains. These findings should be broadly applicable in ongoing vaccine development pipelines, where efficient isolation and purification of large quantities of O antigen is of critical importance. Keywords: Paratyphi A; O antigen, biosynthesis; glycosyltransferase; WbaV; paratose