The extracellular bacterial HtrA proteins as potential therapeutic targets and vaccine candidates
Joanna Skórko-Glonek , Donata Figaj , Urszula Zarzecka , Tomasz Przepióra , Joanna Renke , Barbara Lipińska
AbstractBackground: 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.
|Journal series||Current Medicinal Chemistry, ISSN 0929-8673|
|Publication size in sheets||1.5|
|Keywords in English||serine protease, allosteric enzyme, bacterial infection, virulence factor, development of vaccine, selective inhibition, designing of therapeutic compounds|
|Score|| = 35.0, 20-12-2017, ArticleFromJournal|
= 40.0, 20-12-2017, ArticleFromJournal
|Publication indicators||: 2016 = 3.249 (2) - 2016=3.508 (5)|
* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.