Perault Andrew I, Chandler Courtney E, Rasko David A, Ernst Robert K, Wolfgang Matthew C, Cotter Peggy A
Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Department of Microbial Pathogenesis, University of Maryland, Baltimore, Baltimore, MD 21201, USA.
Cell Host Microbe. 2020 Oct 7;28(4):534-547.e3. doi: 10.1016/j.chom.2020.06.019. Epub 2020 Aug 4.
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.
铜绿假单胞菌和洋葱伯克霍尔德菌复合体（Bcc）菌种是囊性纤维化（CF）患者的机会性肺部病原体。虽然铜绿假单胞菌可在较年轻的CF患者中引发长期感染，但Bcc感染仅出现在青少年和成年人中。铜绿假单胞菌和Bcc都利用VI型分泌系统（T6SSs）来介导细菌间竞争。在此，我们发现来自青少年和成年CF患者的铜绿假单胞菌分离株，而非来自年轻CF患者的分离株，在T6SS依赖的方式下被流行的Bcc分离株洋葱伯克霍尔德菌AU1054菌株击败。易感铜绿假单胞菌分离株的基因组含有T6SS缺失突变，在某些情况下，这些突变的修复使分离株产生抗性。此外，八株Bcc菌株中的七株击败了从同一患者分离出的铜绿假单胞菌菌株。我们的研究结果表明，铜绿假单胞菌适应CF肺部时出现的某些突变会消除T6SS活性，使铜绿假单胞菌及其人类宿主易受潜在致命的Bcc二重感染。
