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Metabolite transfer with the fermentation product 2,3-butanediol enhances virulence by Pseudomonas aeruginosa
Arvind Venkataraman1, Miriam A Rosenbaum2, Jeffrey J Werner3
1Department of Biological and Environmental Engineering, Cornell University, Ithaca, NY 14853, USA.
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.
Insights
Fermentation products from bacteria significantly boost Pseudomonas aeruginosa virulence in cystic fibrosis (CF) airways. Metabolite transfer, especially 2,3-butanediol, enhances pathogen survival and disease progression.
Area of Science:
- Microbiology
- Infectious Diseases
- Cystic Fibrosis Research
Background:
- Cystic fibrosis (CF) airways host persistent microbial communities, with Pseudomonas aeruginosa as a key pathogen.
- Interactions between microbes in polymicrobial CF infections are crucial but poorly understood.
- Understanding these interactions is vital for developing effective CF treatments.
Purpose of the Study:
- To investigate how fermentation products from co-habitant bacteria influence P. aeruginosa virulence.
- To elucidate the metabolic relationship between fermenting bacteria and P. aeruginosa in CF airways.
- To determine the impact of interbacterial metabolite transfer on P. aeruginosa pathogenesis.
Main Methods:
- In vitro experiments exposing P. aeruginosa to common bacterial fermentation products.
- Quantification of virulence factor production, antimicrobial activity, and biofilm formation.
- Analysis of gene expression, specifically the LasI/LasR quorum-sensing system.
Main Results:
- Fermentation products, particularly 2,3-butanediol, significantly increased P. aeruginosa virulence factors, antimicrobial activity, and biofilm formation compared to glucose.
- 2,3-butanediol acts as a substrate for P. aeruginosa, establishing a metabolic link.
- Upregulation of the LasI/LasR quorum-sensing system by 2,3-butanediol led to increased phenazine and exotoxin concentrations and enhanced biofilm.
Conclusions:
- The success of P. aeruginosa in CF airways is influenced by its position in the microbial food web and interactions with fermenting bacteria.
- Interbacterial metabolite transfer significantly stimulates P. aeruginosa virulence.
- These findings suggest that targeting metabolic interactions could impact CF disease progression.
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