Affiliation:
1. Department of Biochemistry, University of Cambridge, Cambridge CB2 1QW, UK
2. Department of Chemistry, Umeå University, 90187, Umeå, Sweden
Abstract
Pseudomonas aeruginosa
is an opportunistic human pathogen and a common cause of chronic infections in individuals with cystic fibrosis (CF). Oxygen limitation was recently reported to regulate the expression of a major virulence determinant in
P. aeruginosa
, the type III secretion system (T3SS). Here, we show that expression of the T3SS in oxygen-limited growth conditions is strongly dependent on the glyoxylate shunt enzyme, isocitrate lyase (ICL; encoded by
aceA
), which was previously shown to be highly expressed in CF isolates. ICL-dependent regulation of the T3SS did not alter the expression level of the master transcriptional regulator, ExsA, but did affect expression of the T3 structural proteins, effectors and regulators (ExsC, ExsD and ExsE). An
aceA
mutant displayed enhanced biofilm formation during anaerobic growth, which suggested that AceA-dependent modulation of type III secretion might impinge upon the RetS/LadS signalling pathways. Indeed, our data suggest that RetS is able to mediate some of its effects through AceA, as expression of
aceA in trans
partially restored T3SS expression in a
retS
mutant. Our findings indicate that AceA is a key player in the metabolic regulation of T3SS expression during oxygen-limited growth of
P. aeruginosa
. To the best of our knowledge, this is the first demonstration that the T3SS can be regulated by factors that do not affect ExsA expression levels.
Subject
General Biochemistry, Genetics and Molecular Biology,Immunology,General Neuroscience
Cited by
24 articles.
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