Investigating the role of a Tannerella forsythia HtrA protease in host protein degradation and inflammatory response.

Autor:	Bloch S; Competence Center for Periodontal Research, University Clinic of Dentistry, Medical University of Vienna, Vienna, Austria.; NanoGlycobiology Research Group, Department of Chemistry, Institute of Biochemistry, Universität für Bodenkultur Wien, Vienna, Austria., Hager-Mair FF; NanoGlycobiology Research Group, Department of Chemistry, Institute of Biochemistry, Universität für Bodenkultur Wien, Vienna, Austria., Bacher J; NanoGlycobiology Research Group, Department of Chemistry, Institute of Biochemistry, Universität für Bodenkultur Wien, Vienna, Austria.; Department of Biotechnology, Institute of Bioprocess Science and Engineering, Universität für Bodenkultur Wien, Vienna, Austria., Tomek MB; NanoGlycobiology Research Group, Department of Chemistry, Institute of Biochemistry, Universität für Bodenkultur Wien, Vienna, Austria., Janesch B; NanoGlycobiology Research Group, Department of Chemistry, Institute of Biochemistry, Universität für Bodenkultur Wien, Vienna, Austria., Andrukhov O; Competence Center for Periodontal Research, University Clinic of Dentistry, Medical University of Vienna, Vienna, Austria., Schäffer C; NanoGlycobiology Research Group, Department of Chemistry, Institute of Biochemistry, Universität für Bodenkultur Wien, Vienna, Austria.
Jazyk:	angličtina
Zdroj:	Frontiers in oral health [Front Oral Health] 2024 Jul 05; Vol. 5, pp. 1425937. Date of Electronic Publication: 2024 Jul 05 (Print Publication: 2024).
DOI:	10.3389/froh.2024.1425937
Abstrakt:	Introduction: Degradation of host proteins by bacterial proteases leads to the subversion of the host response and disruption of oral epithelial integrity, which is considered an essential factor in the progression of periodontitis. High-temperature requirement A (HtrA) protease, which is critical for bacterial survival and environmental adaptation, is found in several oral bacteria, including the periodontal pathogen Tannerella forsythia . This study investigated the proteolytic activity of HtrA from T. forsythia and its ability to modulate the host response. Methods: HtrA of T. forsythia was identified bioinformatically and produced as a recombinant protein. T. forsythia mutants with depleted and restored HtrA production were constructed. The effect of T. forsythia wild-type, mutants and recombinant HtrA on the degradation of casein and E-cadherin was tested in vitro . Additionally, the responses of human gingival fibroblasts and U937 macrophages to the different HtrA-stimuli were investigated and compared to those triggered by the HtrA-deficient mutant. Results: T. forsythia wild-type producing HtrA as well as the recombinant enzyme exhibited proteolytic activity towards casein and E-cadherin. No cytotoxic effect of either the wild-type, T. forsythia mutants or rHtrA on the viability of host cells was found. In hGFB and U937 macrophages, both T. forsythia species induced an inflammatory response of similar magnitude, as indicated by gene and protein expression of interleukin (IL)-1β, IL-6, IL-8, tumour necrosis factor α and monocyte chemoattractant protein (MCP)-1. Recombinant HtrA had no significant effect on the inflammatory response in hGFBs, whereas in U937 macrophages, it induced a transient inflammatory response at the early stage of infection. Conclusion: HtrA of T. forsythia exhibit proteolytic activity towards the host adhesion molecule E-cadherin and has the potential to influence the host response. Its role in the progression of periodontitis needs further clarification. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. (© 2024 Bloch, Hager-Mair, Bacher, Tomek, Janesch, Andrukhov and Schäffer.)
Databáze:	MEDLINE
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