Host Adaptation Predisposes Pseudomonas aeruginosa to Type VI Secretion System-Mediated Predation by the Burkholderia cepacia Complex

Pseudomonas aeruginosa and Burkholderia cepacia complex (Bcc) species are opportunistic lung pathogens of cystic fibrosis (CF) patients. While P. aeruginosa can initiate long-term infections in younger CF patients, Bcc infections only arise in teenagers and adults. Both P. aeruginosa and Bcc use type VI secretion systems (T6SSs) to mediate interbacterial competition. Here, we show P. aeruginosa isolates from teenage and adult CF patients, but not those from young CF patients, are outcompeted by the epidemic Bcc isolate Burkholderia cenocepacia strain AU1054 in a T6SS-dependent manner. The genomes of susceptible P. aeruginosa isolates harbor T6SS-abrogating mutations, the repair of which, in some cases, rendered the isolates resistant. Moreover, seven of eight Bcc strains outcompeted P. aeruginosa strains isolated from the same patients. Our findings suggest certain mutations that arise as P. aeruginosa adapts to the CF lung abrogate T6SS activity, making P. aeruginosa and its human host susceptible to potentially fatal Bcc superinfection. [Display omitted] •Bcc pathogens produce functional antibacterial T6SSs•Bcc pathogens use T6SSs to outcompete host-adapted P. aeruginosa CF isolates•Host-adapted P. aeruginosa CF isolates harbor T6SS-abrogating mutations•T6SS-mediated competition dynamics may restrict Bcc infections to older CF patients Pseudomonas aeruginosa infects cystic fibrosis (CF) patients of all ages. Burkholderia cepacia complex (Bcc) infections are restricted to teenage/adult CF patients. Perault et al. demonstrate Bcc pathogens, using the type VI secretion system (T6SS), only outcompete host-adapted P. aeruginosa isolates, which become T6SS deficient during evolution within the CF respiratory tract.