title: Transcriptional induction of the Pseudomonas aeruginosa type III secretion system by low Ca2+ and host cell contact proceeds through two distinct signaling pathways.
abstract: The opportunistic pathogen Pseudomonas aeruginosa utilizes a type III secretion system (T3SS) to intoxicate eukaryotic host cells. Transcription of the T3SS is induced under calcium-limited growth conditions or following intimate contact of P. aeruginosa with host cells. In the present study, we demonstrate that expression of the T3SS is controlled by two distinct regulatory mechanisms and that these mechanisms are differentially activated in a host cell-dependent manner. The first mechanism is dependent upon ExsC, a regulatory protein that couples transcription of the T3SS to the activity of the type III secretion machinery. ExsC is essential for induction of the T3SS under low-calcium-growth conditions and for T3SS-dependent cytotoxicity towards social amoebae, insect cells, and erythrocytes. The second regulatory mechanism functions independently of ExsC and is sufficient to elicit T3SS-dependent cytotoxicity towards certain types of mammalian cells. Although this second pathway (ExsC independent) is sufficient, an exsC mutant demonstrates a lag in the induction of cytotoxicity towards Chinese hamster ovary cells and is attenuated for virulence in a mouse pneumonia model. We propose that the ExsC-dependent pathway is required for full cytotoxicity towards all host cell types tested whereas the ExsC-independent pathway may represent an adaptation that allows P. aeruginosa to increase expression of the T3SS in response to specific types of mammalian cells.
authors.affiliation: Department of Microbiology, 540B Eckstein Medical Research Building, University of Iowa, Iowa City, IA 52242-1101, USA.
authors.forename: Nandini
authors.initials: N
authors.lastname: Dasgupta
authors.forename: Alix
authors.initials: A
authors.lastname: Ashare
authors.forename: Gary W
authors.initials: GW
authors.lastname: Hunninghake
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Yahr
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000502:physiology; D016466:CHO Cells; D002118:Calcium / Q000502:physiology*; D002450:Cell Communication; D006224:Cricetinae; D002373:Cyclic AMP Receptor Protein / Q000502:physiology; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000472:pathogenicity*; D012097:Repressor Proteins / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology; D014158:Transcription, Genetic; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D002373:Cyclic AMP Receptor Protein; C470740:ExsD protein, Pseudomonas aeruginosa; D012097:Repressor Proteins; D014157:Transcription Factors; C091090:Vfr protein, Pseudomonas aeruginosa; D002118:Calcium