AUTHOR=Xu Xiaohong , Chen Junwei , Huang Xiaoxing , Feng Shunhang , Zhang Xiaoyan , She Feifei , Wen Yancheng 

TITLE=The Role of a Dipeptide Transporter in the Virulence of Human Pathogen, Helicobacter pylori

JOURNAL=Frontiers in Microbiology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2021.633166

DOI=10.3389/fmicb.2021.633166

ISSN=1664-302X

ABSTRACT=<p><italic>Helicobacter pylori</italic> harbors a dipeptide (Dpp) transporter consisting of a substrate-binding protein (DppA), two permeases (DppB and C), and two ATPases (DppD and F). The Dpp transporter is responsible for the transportation of dipeptides and short peptides. We found that its expression is important for the growth of <italic>H</italic>. <italic>pylori</italic>. To understand the role of the Dpp transporter in the pathogenesis of <italic>H</italic>. <italic>pylori</italic>, the expression of virulence factors and <italic>H</italic>. <italic>pylori</italic>-induced IL-8 production were investigated in <italic>H. pylori</italic> wild-type and isogenic <italic>H. pylori</italic> Dpp transporter mutants. We found that expression of CagA was downregulated, while expression of type 4 secretion system (T4SS) components was upregulated in Dpp transporter mutants. The DppA mutant strain expressed higher levels of outer membrane proteins (OMPs), including BabA, HopZ, OipA, and SabA, and showed a higher adhesion level to gastric epithelial AGS cells compared with the <italic>H</italic>. <italic>pylori</italic> 26695 wild-type strain. After infection of AGS cells, <italic>H</italic>. <italic>pylori</italic> Δ<italic>dppA</italic> induced a higher level of NF-κB activation and IL-8 production compared with wild-type. These results suggested that in addition to supporting the growth of <italic>H</italic>. <italic>pylori</italic>, the Dpp transporter causes bacteria to alter the expression of virulence factors and reduces <italic>H</italic>. <italic>pylori</italic>-induced NF-κB activation and IL-8 production in gastric epithelial cells.</p>