Abstract
Helicobacter pullorum is a human zoonotic pathogen transmitted through poultry where it is associated with vibrionic hepatitis and colitis. Hemolysin co-regulated protein (Hcp) is an important structural as well as effector protein of type six secretory system; however, its role in H. pullorum invasion and pathogenesis has not been elucidated. In this study, we predicted the Helicobacter pullorum Hcp (HpuHcp) structure and identified Campylobacter jejuni Hcp (CjHcp) as its nearest homologue. Analysis of the predicted structure shows several common bacterial Hcp motifs like Protein kinase C phosphorylation site, Casein kinase II phosphorylation site, N-myristoylation site, cAMP-and cCGMP-dependent protein kinase phosphorylation site, N-glycosylation site. The presence of unique microbodies C-terminal targeting signal domain was present in HpuHcp which was seen for the first time in CjHcp. This could indicate that Hcp is a structural protein as well as a secretory protein. Moreover, the presence of a deamidase domain, similar to the tecA of Burkholderia cenocepacia an opportunistic pathogen, may help in bacterial internalization as it depolymerises the membranous actin by deamidation of the host cell Rho GTPases cdc42 and Rac1, which was supported by increased invasion of hepatocytes by Hcp-positive isolates.
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Funding
The research work described in this study was supported by the HEC-NRPU fund, Grant No. 7902/Federal/NRPU/R&D/HEC/2017.
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KJ contributed to experimental design, experimental work, in silico analysis and initial drafting of manuscript. FG collected samples and performed experimental work. SB contributed to the in silico analysis, writing and editing of the manuscript. HB and ZN contributed to initial concept, editing of the manuscript. RA contributed in the experimental design and experimental work. SJ contributed to the experimental design, writing and editing of the manuscript.
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Ethical approval for the study for research involving animals for obtaining biological material (bacterial caecal isolates and data) was sought through the COMSATS Institute for Information Technology ethics review board (CIIT ERB), letter number CIIT/Bio/ERB/16/47.
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Supplementary figure 1: Structure of HpuHcp, indicating structural amino acids in yellow barrels with red labels and cyan barrels with black labels are those amino acids which are functional in nature. Table explaining the nature of residues as structural or functional (PDF 65 kb)
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Javed, K., Gul, F., Abbasi, R. et al. In Silico and In Vitro Analysis of Helicobacter pullorum Type Six Secretory Protein Hcp and Its Role in Bacterial Invasion and Pathogenesis. Curr Microbiol 79, 195 (2022). https://doi.org/10.1007/s00284-022-02892-8
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DOI: https://doi.org/10.1007/s00284-022-02892-8