HtrA chaperone activity contributes to host cell binding in Campylobacter jejuni

The aim of this study was to determine the role of the dual activities of HtrA in host cell interaction of C. jejuni by comparing an htrA mutant lacking protease activity, but retaining chaperone activity, with a ΔhtrA mutant and the wild type strain. Binding of C. jejuni to both epithelial cells and macrophages was facilitated mainly by HtrA chaperone activity that may be involved in folding of outer membrane adhesins. In contrast, HtrA protease activity played only a minor role in interaction with host cells.We show that HtrA protease and chaperone activities contribute differently to C. jejuni's interaction with mammalian host cells, with the chaperone activity playing the major role in host cell binding.The enteric pathogen Campylobacter jejuni is a frequent cause of bacterial food-borne infections worldwide [1]. Acute gastroenteritis caused by C. jejuni is characterized by watery or bloody diarrhea, abdominal pain, fever, and malaise. While these symptoms typically last 3 - 7 days, serious complications may follow such as the acute autoimmune disease Guillan Barré Syndrome, affecting the peripheral nervous system. To cause disease in humans, C. jejuni must penetrate the mucus layer of the gastrointestinal epithelium and interact with the underlying epithelial cells [2]. The importance of epithelial cell invasion in disease has been demonstrated in infected humans and animals [3,4], and is emphasized by studies showing that C. jejuni mutants attenuated for virulence in animal models are less capable of invading intestinal epithelial cells in vitro [5,6]. Upon invasion by C. jejuni, human epithelial cells respond by secreting cytokines, such as IL-8, which stimulate recruitment of inflammatory cells [2], including macrophages and dendritic cells that engulf and rapidly kill C. jejuni [7]. Adherence to epithelial cells is a prerequisite for invasion, and capsular polysaccharides, motility, and a number of surface associated proteins including CadF, CapA, JlpA and