Pathogens (Jun 2019)

Characterisation of the Major Extracellular Proteases of <em>Stenotrophomonas maltophilia</em> and Their Effects on Pulmonary Antiproteases

  • Kevin Molloy,
  • Stephen G. Smith,
  • Gerard Cagney,
  • Eugene T. Dillon,
  • Catherine M. Greene,
  • Noel G. McElvaney

DOI
https://doi.org/10.3390/pathogens8030092
Journal volume & issue
Vol. 8, no. 3
p. 92

Abstract

Read online

Stenotrophomonas maltophilia is an emerging global opportunistic pathogen that has been appearing with increasing prevalence in cystic fibrosis (CF). A secreted protease from S. maltophilia has been reported as its chief potential virulence factor. Here, using the reference clinical strain S. maltophilia K279a, the major secreted proteases were identified. Protein biochemistry and mass spectrometry were carried out on K279a culture supernatant. The effect of K279a culture supernatant on cleavage and anti-neutrophil elastase activity of the three majors pulmonary antiproteases was quantified. A deletion mutant of S. maltophilia lacking expression of a protease was constructed. The serine proteases StmPR1, StmPR2 and StmPR3, in addition to chitinase A and an outer membrane esterase were identified in culture supernatants. Protease activity was incompletely abrogated in a K279a-ΔStmPR1: Erm mutant. Wild type K279a culture supernatant degraded alpha-1 antitrypsin (AAT), secretory leucoprotease inhibitor (SLPI) and elafin, important components of the lung’s innate immune defences. Meanwhile SLPI and elafin, but not AAT, retained their ability to inhibit neutrophil elastase. StmPR3 together with StmPR1 and StmPR2, is likely to contribute to protease-mediated innate immune dysfunction in CF.

Keywords