title: A novel anti-anti-activator mechanism regulates expression of the Pseudomonas aeruginosa type III secretion system.
abstract: Expression of the Pseudomonas aeruginosa type III secretion system (TTSS) is coupled to the secretion status of the cells. Environmental signals such as calcium depletion activate the type III secretion channel and, as a consequence, type III gene transcription is derepressed. Two proteins, ExsA and ExsD, were shown previously to play a role in coupling transcription to secretion. ExsA is an activator of TTSS gene transcription, and ExsD is an anti-activator of ExsA. In the absence of environmental secretion cues, ExsD binds ExsA and inhibits transcription. Here, we describe the characterization of ExsC as an anti-anti-activator of TTSS expression. Transcription of the TTSS is repressed in an exsC mutant and is derepressed upon ExsC overexpression. The dependence on exsC for transcription is relieved in the absence of exsD, suggesting that ExsC and ExsD function together to regulate transcription. Consistent with this idea, ExsC interacts with ExsD in bacterial two-hybrid and co-purification assays. We propose a model in which the anti-anti-activator (ExsC) binds to and sequesters the anti-activator (ExsD) under low Ca(2+) conditions, freeing ExsA and allowing for transcription of the TTSS. The P. aeruginosa system represents the first example of an anti-activator/anti-anti-activator pair controlling transcription of a TTSS.
authors.affiliation: Department of Microbiology, W. M. Keck Microbial Communities and Cell Signaling Program, University of Iowa, 540B Eckstein Medical Research Building, Iowa City, IA 52242, USA.
authors.forename: Nandini
authors.initials: N
authors.lastname: Dasgupta
authors.forename: Guinevere L
authors.initials: GL
authors.lastname: Lykken
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Wolfgang
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Yahr
mesh_terms: D015964:Gene Expression Regulation, Bacterial; D021381:Protein Transport; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: C470740:ExsD protein, Pseudomonas aeruginosa; D012097:Repressor Proteins; D015534:Trans-Activators