title: The Extracellular Bacterial HtrA Proteins as Potential Therapeutic Targets and Vaccine Candidates.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of General and Medical Biochemistry, Faculty of Biology, University of Gdansk, Wita Stwosza 59, 80-308 Gdańsk. Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Skórko-Glonek
authors.affiliation: Department of General and Medical Biochemistry, Faculty of Biology, University of Gdansk, Wita Stwosza 59, 80-308 Gdańsk. Poland.
authors.forename: Donata
authors.initials: D
authors.lastname: Figaj
authors.affiliation: Department of General and Medical Biochemistry, Faculty of Biology, University of Gdansk, Wita Stwosza 59, 80-308 Gdańsk. Poland.
authors.forename: Urszula
authors.initials: U
authors.lastname: Zarzecka
authors.affiliation: Department of General and Medical Biochemistry, Faculty of Biology, University of Gdansk, Wita Stwosza 59, 80-308 Gdańsk. Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Przepiora
authors.affiliation: Department of General and Medical Biochemistry, Faculty of Biology, University of Gdansk, Wita Stwosza 59, 80-308 Gdańsk. Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Renke
authors.affiliation: Department of General and Medical Biochemistry, Faculty of Biology, University of Gdansk, Wita Stwosza 59, 80-308 Gdańsk. Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Lipinska
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001419:Bacteria / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology; D001424:Bacterial Infections / Q000188:drug therapy / Q000382:microbiology* / Q000517:prevention & control*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D001428:Bacterial Vaccines / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D055808:Drug Discovery; D006801:Humans; D008958:Models, Molecular; D058990:Molecular Targeted Therapy; D011487:Protein Conformation; D057057:Serine Proteases / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D015842:Serine Proteinase Inhibitors; D057057:Serine Proteases
keywords: Serine protease; allosteric enzyme; bacterial infection; designing of therapeutic compounds; development of vaccine; selective
  inhibition; virulence factor