The Extracellular Bacterial HtrA Proteins as Potential Therapeutic Targets and Vaccine Candidates

Title:The Extracellular Bacterial HtrA Proteins as Potential Therapeutic Targets and Vaccine Candidates

Volume: 24 Issue: 20

Author(s): Joanna Skórko-Glonek*, Donata Figaj, Urszula Zarzecka, Tomasz Przepiora, Joanna Renke and Barbara Lipinska

Affiliation:

• Department of General and Medical Biochemistry, Faculty of Biology, University of Gdansk, Wita Stwosza 59, 80-308 Gdańsk,Poland

Keywords: Serine protease, allosteric enzyme, bacterial infection, virulence factor, development of vaccine, selective inhibition, designing of therapeutic compounds.

Abstract: Background: An increasing resistance of bacteria to the commonly used antimicrobials forces to search for alternative or supportive ways to cure infections. Targeting virulence factors is one of such approaches. The bacterial HtrA proteins are strongly involved in virulence and the lack of functional HtrA in many cases impairs invasiveness of pathogens. HtrAs act by protecting the cells under stressful conditions as well as they take direct part in invasion of the host. The latter function is played predominantly by the recently identified extracellular fraction of HtrA. This review aims to evaluate HtrAs as therapeutic targets, including design of chemical inhibitors and vaccines.

Methods: We undertook a thorough search of bibliographic databases for peer-reviewed scientific literature.

Results: One hundred and sixty-four papers were included in the review. First, we briefly summarized key structural and functional properties of known HtrA proteins with the special focus on the extracellular HtrA fraction. Then we provided an overview of efforts and advancements to target HtrAs of pathogenic bacteria as a promising antimicrobial therapy. In some cases, encouraging results were obtained and application of HtrAspecific inhibitors protected tissues from damage and killed bacteria. Also promising reports concerning the use of HtrA as a protective antigen in several disease models have recently been published.

Conclusion: The findings of this review suggest that the exported HtrA proteins are very attractive therapeutic targets due to their accessibility, significance in virulence and immunogenicity. However, further extensive studies are still needed to develop a safe antimicrobial treatment.

Cite this article as:

Skórko-Glonek Joanna*, Figaj Donata, Zarzecka Urszula, Przepiora Tomasz, Renke Joanna and Lipinska Barbara, The Extracellular Bacterial HtrA Proteins as Potential Therapeutic Targets and Vaccine Candidates, Current Medicinal Chemistry 2017; 24 (20) . https://dx.doi.org/10.2174/0929867323666161223145825

DOI https://dx.doi.org/10.2174/0929867323666161223145825	Print ISSN 0929-8673
Publisher Name Bentham Science Publisher	Online ISSN 1875-533X