Stenotrophomonas maltophilia encodes a type II protein secretion system that promotes detrimental effects on lung

Sara M Karaba1, Richard C White, Nicholas P Cianciotto

  • 1Department of Microbiology and Immunology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

Insights

Stenotrophomonas maltophilia uses a type II protein secretion (T2S) system, known as Xps, to secrete virulence factors. This system is crucial for its ability to damage lung cells and is a key factor in its pathogenesis.

Area of Science:

  • Microbiology
  • Bacterial Pathogenesis
  • Molecular Biology

Background:

  • Stenotrophomonas maltophilia is a multidrug-resistant bacterium causing significant infections like pneumonia.
  • The molecular mechanisms underlying S. maltophilia virulence are poorly understood.
  • Understanding virulence factors is critical for combating antibiotic resistance.

Purpose of the Study:

  • To investigate the role of protein secretion systems in S. maltophilia virulence.
  • To characterize the function of the type II protein secretion (T2S) system in S. maltophilia strain K279a.
  • To determine the contribution of T2S to the bacterium's pathogenic effects on human lung cells.

Main Methods:

  • Genetic analysis of S. maltophilia strain K279a, focusing on the xps locus.
  • Construction and characterization of mutants in the T2S system.
  • Assessing the impact of secreted proteins on A549 human lung epithelial cells.
  • Evaluating host cell responses, including cell rounding, detachment, death, and actin cytoskeleton rearrangement.
  • Complementation assays to confirm the role of specific genes.

Main Results:

  • A functional type II protein secretion (T2S) system, designated Xps, was identified in S. maltophilia K279a.
  • Mutants lacking functional Xps T2S exhibited significantly reduced secretion of proteins and proteolytic activities.
  • Supernatants from xps mutants failed to induce characteristic cytotoxic effects on A549 lung cells, including cell rounding, detachment, death, and actin cytoskeleton disruption.
  • The Xps T2S system was essential for S. maltophilia's detrimental impact on host cells.
  • A second T2S system (Gsp) was found to be cryptic under tested conditions.
  • Xps-dependent activities were observed in other clinical isolates of S. maltophilia.

Conclusions:

  • The Xps type II protein secretion system is a key virulence factor in Stenotrophomonas maltophilia.
  • Xps T2S is required for the secretion of proteins that mediate cytotoxic effects on human lung epithelial cells.
  • This study provides the first detailed examination of T2S in S. maltophilia, highlighting its significant role in pathogenesis.

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