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.Keywords: Serine protease, allosteric enzyme, bacterial infection, virulence factor, development of vaccine, selective inhibition, designing of therapeutic compounds.
Current Medicinal Chemistry
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.Export Options
About this article
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 |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
![](/images/wayfinder.jpg)
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Follow-Up Study of Olfactory Deficits, Cognitive Functions, and Volume Loss of Medial Temporal Lobe Structures in Patients with Mild Cognitive Impairment
Current Alzheimer Research The Role and Mechanism of Thiol-Dependent Antioxidant System in Bacterial Drug Susceptibility and Resistance
Current Medicinal Chemistry Immunological Mechanisms of Neuropsychiatric Lupus
Current Immunology Reviews (Discontinued) Vasculogenic and Angiogenic Pathways in Moyamoya Disease
Current Medicinal Chemistry Heat Shock Protein Inhibitors for the Treatment of Fungal Infections
Recent Patents on Anti-Infective Drug Discovery Biopharmaceutics, Pharmacokinetics and Pharmacodynamics of Antituberculosis Drugs
Current Medicinal Chemistry MRI of Central Nervous System (CNS) Vasculitis
Current Medical Imaging The Possibilities and Pitfalls for Anti-Complement Therapies in Inflammatory Diseases
Current Drug Targets - Inflammation & Allergy Current Treatment Strategies for Multiple Sclerosis - Efficacy Versus Neurological Adverse Effects
Current Pharmaceutical Design Antifungal Azole Derivatives and their Pharmacological Potential: Prospects & Retrospects
The Natural Products Journal Bacteriophages as Therapeutic and Prophylactic Means: Summary of the Soviet and Post Soviet Experiences
Current Drug Delivery Pathology of Multiple Sclerosis
CNS & Neurological Disorders - Drug Targets Pharmacogenomics and Severe Infections: The Role of the Genomes of Both the Host and the Pathogen
Current Pharmacogenomics <i>Corynebacterium Striatum</i>, an Emerging Nosocomial Pathogen: Case Reports
Infectious Disorders - Drug Targets A 30-years Review on Pharmacokinetics of Antibiotics: Is the Right Time for Pharmacogenetics?
Current Drug Metabolism Isolation of <i>Morganella Morganii</i> and <i>Providencia</i> Species from Clinical Samples in a Tertiary Care Hospital in North India
Infectious Disorders - Drug Targets Diabetes Mellitus and Bell’s Palsy
Current Diabetes Reviews Bone Imaging in Metastatic Castration-resistant Prostate Cancer; Where do we Stand
Current Radiopharmaceuticals Recent Advances in Analytical Techniques used for the Determination of Fluoroquinolones in Pharmaceuticals and Samples of Biological Origin - A Review Article
Current Pharmaceutical Analysis Pharmacotherapy of Sickle Cell Disease in Children
Current Pharmaceutical Design