## 7 Mechanistic and Molecular Concepts and Their Significant Role in Disease Manifestation
Interestingly, this inflammatory response necessitates an operational alpha kinase-1 (ALPK-1) receptor while it proceeds independently of the TLR and NOD-like receptor (NLR) signaling pathways. Furthermore, the intracellular peptidoglycan receptors NOD-1 and NOD-2, along with the NLRP-3 inflammasome, detect the intrusion of _C. jejuni_ and initiate innate immune responses [77]. The discovery of ADP-heptose as a powerful and novel pro-inflammatory agent marks the unveiling of a previously unidentified virulence factor of _C. jejuni_, which may play a significant role in developing enteritis. These findings designate ADP-heptose and its related heptose phosphates as possible important virulence determinants in _C. jejuni_, playing a crucial role in the bacterium's pathogenicity during human infections. Consequently, these compounds are recognized as significant virulence factors, contributing to acute human enteric infections by activating the ALPK1-NF-kB pro-inflammatory pathway [77]. Novel advancements in electron and confocal immunofluorescence microscopy have unveiled insightful details regarding the _HtrA_-dependent disruption of the intestinal epithelium by _C. jejuni_[78]. Investigations have demonstrated that _C. jejuni_ bacteria expressing HtrA can induce substantial damage to cellular junctions, a phenomenon not replicated by either soluble purified _HtrA_ or _HtrA_-containing outer-membrane vesicles (OMVs), even at concentrations significantly exceeding physiological levels [78]. The research further revealed that only those bacterial cells engaged in active protein biosynthesis can effectively cleave junctional proteins. This process precedes the paracellular transmigration of _C. jejuni_ across the epithelial barrier. These disclosures highlight the compulsory role of _HtrA_ in the pathogenic mechanisms employed by _C. jejuni_ and provide a deeper understanding of its virulence strategies [78]. The frequency of strains possessing genes responsible for the sialylation of LOS among patients suffering from human enteric diseases appears to fluctuate between 50% and 60% [79]. Autoimmune responses in campylobacteriosis are triggered by antibodies targeting LOS from the _Campylobacter_ cell wall, which cross-react with specific sugar moieties on host cell targets [80]. Moreover, particular sialylated LOS structures influence the intensity of acute campylobacteriosis and the likelihood of developing post-infectious sequelae [80]. The LOS of _C. jejuni_ functions as an endotoxin, engaging the innate immune system via the activation of TLR-4 and subsequent signaling cascades, including pathways regulated by the mammalian target of rapamycin (mTOR). This interaction prompts apoptotic mechanisms within the intestinal epithelia following _C. jejuni_ adhesion and invasion. Inflammation in this context is predominantly driven by cytokines such as interleukin-6 (IL-6), IFN-\(\gamma\) and TNF-\(\alpha\), outlining the complex interplay between bacterial factors and the host's immune response in the pathology of campylobacteriosis [80]. The activity of sialyltransferase (cstII) significantly contributes to the pathogenicity of _Campylobacter_ by endowing its LOS with a protective shield that aids in the disruption of epithelial cells, an action reminiscent of human ganglioside-induced diarrhea [11]. The gene _vlaN_ plays a crucial role in the synthesis of LPS. The _spoT_ gene is pivotal for stringent response regulation, and the catalase _KatA_ gene is essential for converting H\({}_{2}\)O\({}_{2}\) into H\({}_{2}\)O and O\({}_{2}\), offering protection against oxidative stress [11]. The genes _cj0012c_ and _cj1371_ also encode proteins that safeguard against reactive oxygen species. The Peb4 chaperone has emerged as another vital virulence mechanism in _Campylobacter_, facilitating the export of proteins to the outer membrane.