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Type III secretion system expression in oxygen-limited Pseudomonas aeruginosa cultures is stimulated by isocitrate

Jade C S Chung1, Olena Rzhepishevska, Madeleine Ramstedt

  • 1Department of Biochemistry, University of Cambridge, Cambridge CB2 1QW, UK.

Open Biology
|February 1, 2013
PubMed

Insights

The glyoxylate shunt enzyme isocitrate lyase (ICL) regulates the type III secretion system (T3SS) in Pseudomonas aeruginosa under oxygen limitation. This metabolic regulation impacts virulence and biofilm formation in this opportunistic pathogen.

Area of Science:

  • Microbiology
  • Bacterial Pathogenesis
  • Metabolic Regulation

Background:

  • Pseudomonas aeruginosa is an opportunistic pathogen causing chronic infections, particularly in cystic fibrosis (CF) patients.
  • Oxygen limitation influences the expression of the type III secretion system (T3SS), a key virulence factor.
  • Isocitrate lyase (ICL), encoded by aceA, is upregulated in CF isolates and linked to T3SS regulation.

Purpose of the Study:

  • To investigate the role of isocitrate lyase (ICL) in regulating type III secretion system (T3SS) expression in Pseudomonas aeruginosa under oxygen-limited conditions.
  • To elucidate the relationship between ICL, T3SS regulation, and other signaling pathways like RetS/LadS.

Main Methods:

  • Analysis of T3SS gene expression in Pseudomonas aeruginosa under varying oxygen levels.
  • Genetic manipulation of aceA and retS genes to assess their impact on T3SS expression and biofilm formation.
  • Investigating the effect of ICL on the expression of T3SS components and regulators (ExsA, ExsC, ExsD, ExsE).

Main Results:

  • ICL (aceA) is essential for T3SS expression during oxygen-limited growth, independent of the master regulator ExsA.
  • ICL affects the expression of T3SS structural proteins and secreted effectors.
  • An aceA mutant shows increased biofilm formation under anaerobic conditions, suggesting a link to RetS/LadS pathways.
  • RetS signaling partially acts through ICL, as aceA expression can restore T3SS expression in a retS mutant.

Conclusions:

  • Isocitrate lyase (ICL) is a critical metabolic regulator of T3SS expression in Pseudomonas aeruginosa during oxygen-limited growth.
  • This study reveals a novel regulatory mechanism for T3SS not dependent on ExsA levels.
  • ICL influences bacterial virulence and biofilm strategies in response to environmental cues.

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