title: Genome-wide analysis of host responses to the Pseudomonas aeruginosa type III secretion system yields synergistic effects.
abstract: The type III secretion system (TTSS) is a dedicated bacterial pathogen protein targeting system that directly affects host cell signalling and response pathways. Our goal was to identify host responses to the Pseudomonas aeruginosa effectors, introduced into target cells utilizing the TTSS. We carried out expression profiling of a human lung pneumocyte cell line A549 exposed to isogenic mutants of P. aeruginosa PAK lacking individual or a combination of TTSS components. We then devised a data analysis method to isolate the key responses to specific secreted bacterial effector proteins as well as components of the TTSS machinery. Individually, the effector proteins elicited host responses consistent with their known functions, many of which were cell cycle-related. However, our analysis has shown that the effector proteins elicit a distinct host transcriptional response when present in combination, suggesting a synergistic effect. Furthermore, the pattern of host transcriptional responses is consistent with the pore forming ability of the TTSS needle complex. This study shows that the individual components of the TTSS define an integrated system and that a systems biology approach is required to fully understand the complex interplay between pathogen and host.
authors.affiliation: Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Jeffrey K
authors.initials: JK
authors.lastname: Ichikawa
authors.forename: Sangeeta B
authors.initials: SB
authors.lastname: English
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Wolfgang
authors.forename: Rebekah
authors.initials: R
authors.lastname: Jackson
authors.forename: Atul J
authors.initials: AJ
authors.lastname: Butte
authors.forename: Stephen
authors.initials: S
authors.lastname: Lory
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D002460:Cell Line; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D016678:Genome; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000378:metabolism / Q000472:pathogenicity*
chemical_list: D001426:Bacterial Proteins; D011506:Proteins