Commensal bacteria can inhibit the growth ofP. aeruginosain cystic fibrosis airway infections through a released metabolite

AbstractIn cystic fibrosis (CF), infections withPseudomonas aeruginosaor other typical pathogens play a critical role in eliciting disease progression, leading to tissue damage and finally loss of lung function. Previous observations showed that the presence of various commensal bacteria and a higher airway microbiome diversity were associated with better lung function and less severe disease burden. Thus, the hypothesis was raised that commensal bacteria might be able to interfere with pathogenic bacteria. In this study, we aimed to identify airway commensal bacteria that inhibit the growth ofP. aeruginosa.Through a screening experiment of co-culture withP. aeruginosaPAO1, we could identify more than 30 CF commensal strains from various species that inhibited the growth ofP. aeruginosa. With multiple selected strains, we further verified the results withP. aeruginosaCF isolates and several other pathogens isolated from CF patients, and most of the identified commensal strains showed consistent results strongly inhibiting the growth of diverse CF pathogens.The underlying mechanisms of the growth-inhibition effects were first investigated through genomic analysis by comparing strains with and without growth-inhibition effects, which revealed that genes responsible for carbohydrate transport and metabolism were highly enriched in the inhibitory commensals. Metabolite analysis and functional analysis showed that commensals with inhibitory effects produce large amounts of acetate. Exogenous addition of acetate under a low pH inhibited the growth ofP. aeruginosa, indicating acetate produced and released by commensals may affect the growth ofP. aeruginosaliving in the same microenvironment.In summary, through co-culture ofP. aeruginosawith commensals, we could identify that a variety of airway commensal strains can inhibit the growth ofP. aeruginosaby producing acetate. The data provide insights into possible novel strategies for controlling infections in people with CF and also emphasize the importance of preserving airway commensals when designing infection treatment strategies.