title: Candida albicans Inhibits Pseudomonas aeruginosa Virulence through Suppression of Pyochelin and Pyoverdine Biosynthesis.
abstract: Bacterial-fungal interactions have important physiologic and medical ramifications, but the mechanisms of these interactions are poorly understood. The gut is host to trillions of microorganisms, and bacterial-fungal interactions are likely to be important. Using a neutropenic mouse model of microbial gastrointestinal colonization and dissemination, we show that the fungus Candida albicans inhibits the virulence of the bacterium Pseudomonas aeruginosa by inhibiting P. aeruginosa pyochelin and pyoverdine gene expression, which plays a critical role in iron acquisition and virulence. Accordingly, deletion of both P. aeruginosa pyochelin and pyoverdine genes attenuates P. aeruginosa virulence. Heat-killed C. albicans has no effect on P. aeruginosa, whereas C. albicans secreted proteins directly suppress P. aeruginosa pyoverdine and pyochelin expression and inhibit P. aeruginosa virulence in mice. Interestingly, suppression or deletion of pyochelin and pyoverdine genes has no effect on P. aeruginosa's ability to colonize the GI tract but does decrease P. aeruginosa's cytotoxic effect on cultured colonocytes. Finally, oral iron supplementation restores P. aeruginosa virulence in P. aeruginosa and C. albicans colonized mice. Together, our findings provide insight into how a bacterial-fungal interaction can modulate bacterial virulence in the intestine. Previously described bacterial-fungal antagonistic interactions have focused on growth inhibition or colonization inhibition/modulation, yet here we describe a novel observation of fungal-inhibition of bacterial effectors critical for virulence but not important for colonization. These findings validate the use of a mammalian model system to explore the complexities of polymicrobial, polykingdom infections in order to identify new therapeutic targets for preventing microbial disease.
authors: Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
authors: Eduardo
authors: E
authors: Lopez-Medina
authors: Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
authors: Di
authors: D
authors: Fan
authors: Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
authors: Laura A
authors: LA
authors: Coughlin
authors: Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
authors: Evi X
authors: EX
authors: Ho
authors: Department of Biochemistry, University of Otago, Dunedin, New Zealand.
authors: Iain L
authors: IL
authors: Lamont
authors: Department of Fundamental Microbiology, University of Lausanne, Lausanne, Switzerland.
authors: Cornelia
authors: C
authors: Reimmann
authors: Department of Immunology, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America; The Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America; Center for Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America; Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
authors: Lora V
authors: LV
authors: Hooper
authors: Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America; Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America; Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
authors: Andrew Y
authors: AY
authors: Koh
mesh_terms: D000818:Animals; D002176:Candida albicans / Q000502:physiology*; D005204:Farnesol / Q000494:pharmacology; D005260:Female; D041981:Gastrointestinal Tract / Q000382:microbiology; D007501:Iron / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009842:Oligopeptides / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D010636:Phenols / Q000037:antagonists & inhibitors*; D011550:Pseudomonas aeruginosa / Q000472:pathogenicity*; D013844:Thiazoles / Q000037:antagonists & inhibitors*; D014774:Virulence
chemical_list: D009842:Oligopeptides; D010636:Phenols; D013844:Thiazoles; D005204:Farnesol; C025316:pyochelin; C042453:pyoverdin; D007501:Iron