Iron bioavailability regulates Pseudomonas aeruginosa interspecies interactions through type VI secretion expression

The cystic fibrosis (CF) respiratory tract harbors pathogenic bacteria that cause life-threatening chronic infections. Of these, Pseudomonas aeruginosa becomes increasingly dominant with age and is associated with worsening lung function and declining microbial diversity. We aimed to understand why P. aeruginosa dominates over other pathogens to cause worsening disease. Here, we show that P. aeruginosa responds to dynamic changes in iron concentration, often associated with viral infection and pulmonary exacerbations, to become more competitive via expression of the TseT toxic effector. However, this behavior can be therapeutically targeted using the iron chelator deferiprone to block TseT expression and competition. Overall, we find that iron concentration and TseT expression significantly correlate with microbial diversity in the respiratory tract of people with CF. These findings improve our understanding of how P. aeruginosa becomes increasingly dominant with age in people with CF and provide a therapeutically targetable pathway to help prevent this shift. [Display omitted] •P. aeruginosa expresses TseT during viral infection in response to increased iron•Iron bioavailability drives TseT-mediated competition in the host environment•Iron chelation reduces TseT expression and prevents TseT-mediated competition•Iron-mediated TseT expression reduces microbiome diversity in people with CF Haas et al. report that respiratory viral infections promote a rise in Pseudomonas aeruginosa infections and associated declining microbiome diversity in people with cystic fibrosis through a mechanism of enhanced TseT-mediated type VI secretion system microbial competition due to increased iron bioavailability.