Investigation of commensal bacteria in controlling Pseudomonas aeruginosa airway infection
Final Report Abstract
Cystic fibrosis (CF) is the most common hereditary lung disease. Among other factors, airway infection is the leading cause for disease progression and loss of lung function. Infections with Pseudomonas aeruginosa or other typical CF pathogens play a critical role in initiating a cycle of infection, inflammation and tissue destruction. However, infections in CF are typical of polymicrobial nature and recent microbiome studies have shown that the airway microbiome diversity, in particular the presence of a variety of commensal bacteria, is positively associated with better lung function and less severe disease. In a previous screening study, from the airways of people with CF, we identified commensal bacteria that are able to inhibit P. aeruginosa and/or reduce pro-inflammatory responses caused by P. aeruginosa infection. In the current project, to understand the mechanism of how commensals affect host responses and inhibit pathogen growth, we applied RNA-seq to acquire information about both bacterial transcriptome and host transcriptome changes. This was carried out through comparing monoinfection and co-infection conditions in precision cut lung slices (PCLS) as an ex-vivo system. Using RNA-seq, first, we were able to identify P. aeruginosa/commensal interaction-triggered transcriptomic changes in bacteria that allowed us to understand how the growth of P. aeruginosa was inhibited by certain commensal strain; second, we could examine the impact of coinfection of P. aeruginosa/commensal on host defenses by comparing host-responses to P. aeruginosa mono-infection and to co-infection. Transcriptome changes in the host in response to co-infection indicated that several signaling pathways mediating inflammatory responses were downregulated by co-infection with S. mitis and P. aeruginosa compared to P. aeruginosa mono-infection, such as neutrophil extracellular trap formation. The underlying mechanisms of how the growth of P. aeruginosa was inhibited by certain commensal strain were investigated via genomic, transcriptomic, metabolic and functional analysis, revealing that the inhibitory commensals affect the growth of P. aeruginosa by releasing a large amount of acetic acid. The results direct further investigations of the commensal-pathogen-host interactions in CF with the aim of using commensal derived compounds as potential therapeutics.
Publications
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Commensal bacteria in cystic fibrosis airway infections modulate growth and inflammation of P. aeruginosa; 44th European Cystic Fibro-Sis Conference 09.06 - 12.06.2021, oral presentation WS01.1
Tony-Odigie A., Boutin S., Dalpke A. & Yi B.
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The impact of Streptococcus on immune response triggered by Pseudomonas aeruginosa infection in the context of cystic fibrosis. Presentation at the 7th Joint Conference Of Dghm & Vaam, virtual meeting, September 12-14, 2021.
Tony-Odigie A., Wilke L., Boutin S., Dalpke A.H. & Yi B.
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Commensal bacteria can inhibit the growth of P. aeruginosa in cystic fibrosis airway infections through a released metabolite.
Tony-Odigie, Andrew; Dalpke, Alexander H.; Boutin, Sébastien & Yi, Buqing
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Airway commensal bacteria in cystic fibrosis inhibit the growth of P. aeruginosa via a released metabolite. Microbiological Research, 283, 127680.
Tony-Odigie, Andrew; Dalpke, Alexander H.; Boutin, Sébastien & Yi, Buqing
