Function of serine protease HtrA in the lifecycle of the foodborne pathogen Campylobacter jejuni

Boehm, Manja; Simson, Daniel; Escher, Ulrike; Schmidt, Anja; Bereswill, Stefan; Tegtmeyer, Nicole; Backert, Steffen; Heimesaat, Markus M.

doi:10.1556/1886.2018.00011

Cited by 32 publications

(30 citation statements)

References 123 publications

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“…HtrA proteases are highly conserved among pathogens and are essential for survival under stress conditions 125 . Extracellular HtrA helps the bacterium to translocate across the epithelium by targeting TJ and adherens proteins, thereby impairing the barrier function 126‐129 . Although the precise role of these proteases in IBD pathogenesis has not been determined, the aforementioned data support the possibility that such peptidases and perhaps others may contribute to one or more steps during the inflammatory response.…”

Section: Gut Microbial Serine Proteasesmentioning

confidence: 99%

Serine proteases at the cutting edge of IBD: Focus on gastrointestinal inflammation

et al. 2020

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Serine proteases have been long recognized to coordinate many physiological processes and play key roles in regulating the inflammatory response. Accordingly, their dysregulation has been regularly associated with several inflammatory disorders and suggested as a central mechanism in the pathophysiology of digestive inflammation. So far, studies addressing the proteolytic homeostasis in the gut have mainly focused on host serine proteases as candidates of interest, while largely ignoring the potential contribution of their bacterial counterparts. The human gut microbiota comprises a complex ecosystem that contributes to host health and disease. Yet, our understanding of microbially produced serine proteases and investigation of whether they are causally linked to IBD is still in its infancy. In this review, we highlight recent advances in the emerging roles of host and bacterial serine proteases in digestive inflammation. We also discuss the application of available tools in the gut to monitor disease‐related serine proteases. An exhaustive representation and understanding of such functional potential would help in closing existing gaps in mechanistic knowledge.

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Section: Gut Microbial Serine Proteasesmentioning

confidence: 99%

Serine proteases at the cutting edge of IBD: Focus on gastrointestinal inflammation

et al. 2020

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“…Campylobacter jejuni has been detected in many tissues, such as lamina propria, and blood. Recently, C. jejuni was reported to cleave cell-to-cell junction factors, such as E-cadherin, and occlude facilitating the invasion of pathogens into IECs via serine protease HtrA and bacterial EVs [56,57]. The toxicity of HtrA proteins and their orthologues are nonnegligible in both prokaryotes and eukaryotes [58].…”

Section: Evs In Ibdmentioning

confidence: 99%

Extracellular Vesicles with Possible Roles in Gut Intestinal Tract Homeostasis and IBD

Chang

Wang

Zhao

et al. 2020

Mediators of Inflammation

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The intestinal tract consists of various types of cells, such as epithelial cells, Paneth cells, macrophages, and lymphocytes, which constitute the intestinal immune system and play a significant role in maintaining intestinal homeostasis by producing antimicrobial materials and controlling the host-commensal balance. Various studies have found that the dysfunction of intestinal homeostasis contributes to the pathogenesis of inflammatory bowel disease (IBD). As a novel mediator, extracellular vesicles (EVs) have been recognized as effective communicators, not only between cells but also between cells and the organism. In recent years, EVs have been regarded as vital characters for dysregulated homeostasis and IBD in either the etiology or the pathology of intestinal inflammation. Here, we review recent studies on EVs associated with intestinal homeostasis and IBD and discuss their source, cargo, and origin, as well as their therapeutic effects on IBD, which mainly include artificial nanoparticles and EVs derived from microorganisms.

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“…In addition, post-infectious complications such as Guillain–Barré syndrome and Miller Fisher syndrome can emerge in a minority of patients (Masanta et al, 2013; Goodfellow and Willison, 2016; Backert et al, 2017). C. jejuni bacteria enter the host intestine via the oral route and colonize the distal ileum and colon by attaching to epithelial cells (Kist and Bereswill, 2001; Boehm et al, 2018). To reach deeper tissues and cause inflammatory responses during the infection process, C. jejuni need to cross the epithelial barrier, which is accomplished by paracellular transmigration as well as invasion into intestinal epithelial cells (Boehm et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Protease Activity of Campylobacter jejuni HtrA Modulates Distinct Intestinal and Systemic Immune Responses in Infected Secondary Abiotic IL-10 Deficient Mice

Schmidt¹,

Escher²,

Mousavi³

et al. 2019

Front. Cell. Infect. Microbiol.

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Even though human Campylobacter jejuni infections are progressively increasing worldwide, the underlying molecular mechanisms of pathogen-host-interactions are still not fully understood. We have recently shown that the secreted serine protease HtrA plays a key role in C. jejuni cellular invasion and transepithelial migration in vitro , and is involved in the onset of intestinal pathology in murine infection models in vivo . In the present study, we investigated whether the protease activity of HtrA had an impact in C. jejuni induced acute enterocolitis. For this purpose, we perorally infected secondary abiotic IL-10 −/− mice with wildtype C. jejuni strain NCTC11168 (11168 WT ) or isogenic bacteria carrying protease-inactive HtrA with a single point mutation at S197A in the active center (11168 HtrA−S197A ). Irrespective of the applied pathogenic strain, mice harbored similar C. jejuni loads in their feces and exhibited comparably severe macroscopic signs of acute enterocolitis at day 6 postinfection (p.i.). Interestingly, the 11168 HtrA−S197A infected mice displayed less pronounced colonic apoptosis and immune cell responses, but enhanced epithelial proliferation as compared to the 11168 WT strain infected controls. Furthermore, less distinct microscopic sequelae in 11168 HtrA−S197A as compared to parental strain infected mice were accompanied by less distinct colonic secretion of pro-inflammatory cytokines such as MCP-1, IL-6, TNF, and IFN-γ in the former as compared to the latter. Strikingly, the S197A point mutation was additionally associated with less pronounced systemic pro-inflammatory immune responses as assessed in serum samples. In conclusion, HtrA is a remarkable novel virulence determinant of C. jejuni , whose protease activity is not required for intestinal colonization and establishment of disease, but aggravates campylobacteriosis by triggering apoptosis and pro-inflammatory immune responses.

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Function of serine protease HtrA in the lifecycle of the foodborne pathogen Campylobacter jejuni

Cited by 32 publications

References 123 publications

Serine proteases at the cutting edge of IBD: Focus on gastrointestinal inflammation

Serine proteases at the cutting edge of IBD: Focus on gastrointestinal inflammation

Extracellular Vesicles with Possible Roles in Gut Intestinal Tract Homeostasis and IBD

Protease Activity of Campylobacter jejuni HtrA Modulates Distinct Intestinal and Systemic Immune Responses in Infected Secondary Abiotic IL-10 Deficient Mice

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