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
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