title: Metabolite transfer with the fermentation product 2,3-butanediol enhances virulence by Pseudomonas aeruginosa.
abstract: The respiratory tract of cystic fibrosis (CF) patients harbor persistent microbial communities (CF airway microbiome) with Pseudomonas aeruginosa emerging as a dominant pathogen. Within a polymicrobial infection, interactions between co-habitant microbes can be important for pathogenesis, but even when considered, these interactions are not well understood. Here, we show with in vitro experiments that, compared with glucose, common fermentation products from co-habitant bacteria significantly increase virulence factor production, antimicrobial activity and biofilm formation of P. aeruginosa. The maximum stimulating effect was produced with the fermentation product 2,3-butanediol, which is a substrate for P. aeruginosa, resulting in a metabolic relationship between fermenters and this pathogen. The global transcription regulator LasI LasR, which controls quorum sensing, was upregulated threefold with 2,3-butanediol, resulting in higher phenazine and exotoxin concentrations and improved biofilm formation. This indicates that the success of P. aeruginosa in CF airway microbiomes could be governed by the location within the food web with fermenting bacteria. Our findings suggest that interbacterial metabolite transfer in polymicrobial infections stimulates virulence of P. aeruginosa and could have a considerable impact on disease progression.
authors.affiliation: Department of Biological and Environmental Engineering, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Arvind
authors.initials: A
authors.lastname: Venkataraman
authors.affiliation: 1] Department of Biological and Environmental Engineering, Cornell University, Ithaca, NY 14853, USA [2] iAMB - Institute of Applied Microbiology, RWTH Aachen University, Aachen, Germany.
authors.forename: Miriam A
authors.initials: MA
authors.lastname: Rosenbaum
authors.affiliation: 1] Department of Biological and Environmental Engineering, Cornell University, Ithaca, NY 14853, USA [2] Department of Chemistry, SUNY Cortland, Bowers Hall, Cortland, NY, USA.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Werner
authors.affiliation: Department of Microbiology, Cornell University, Ithaca, NY, USA.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Winans
authors.affiliation: Department of Biological and Environmental Engineering, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Largus T
authors.initials: LT
authors.lastname: Angenent
mesh_terms: D018441:Biofilms; D002072:Butylene Glycols / Q000378:metabolism*; D005285:Fermentation; D011550:Pseudomonas aeruginosa / Q000378:metabolism / Q000472:pathogenicity* / Q000502:physiology; D053038:Quorum Sensing; D014774:Virulence; D037521:Virulence Factors / Q000378:metabolism
chemical_list: D002072:Butylene Glycols; D037521:Virulence Factors; C026978:2,3-butylene glycol