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Cell Microbiol. 2018 Jun;20(6):e12845. doi: 10.1111/cmi.12845. Epub 2018 Apr 30.

Extracellular HtrA serine proteases: An emerging new strategy in bacterial pathogenesis.

Author information

1
Department of Biology, Division of Microbiology, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
2
Department of Biosciences, Division of Microbiology, Paris Lodron University of Salzburg, Salzburg, Austria.
3
Department of General and Medical Biochemistry, Faculty of Biology, University of Gdansk, Gdansk, Poland.

Abstract

The HtrA family of chaperones and serine proteases is important for regulating stress responses and controlling protein quality in the periplasm of bacteria. HtrA is also associated with infectious diseases since inactivation of htrA genes results in significantly reduced virulence properties by various bacterial pathogens. These virulence features of HtrA can be attributed to reduced fitness of the bacteria, higher susceptibility to environmental stress and/or diminished secretion of virulence factors. In some Gram-negative and Gram-positive pathogens, HtrA itself can be exposed to the extracellular environment promoting bacterial colonisation and invasion of host tissues. Most of our knowledge on the function of exported HtrAs stems from research on Helicobacter pylori, Campylobacter jejuni, Borrelia burgdorferi, Bacillus anthracis, and Chlamydia species. Here, we discuss recent progress showing that extracellular HtrAs are able to cleave cell-to-cell junction factors including E-cadherin, occludin, and claudin-8, as well as extracellular matrix proteins such as fibronectin, aggrecan, and proteoglycans, disrupting the epithelial barrier and producing substantial host cell damage. We propose that the export of HtrAs is a newly discovered strategy, also applied by additional bacterial pathogens. Consequently, exported HtrA proteases represent highly attractive targets for antibacterial treatment by inhibiting their proteolytic activity or application in vaccine development.

KEYWORDS:

E-cadherin; HtrA; OMV; adherens junction; aggrecan; chaperone; claudin; fibronectin; infection biology; occludin; outer membrane vesicles; proteoglycan; secretion; serine protease; tight junction

PMID:
29582532
DOI:
10.1111/cmi.12845

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