Transcriptional Response of Mucoid Pseudomonas aeruginosa to Human Respiratory Mucus

Adaptation of bacterial pathogens to a host can lead to the selection and accumulation of specific mutations in their genomes with profound effects on the overall physiology and virulence of the organisms. The opportunistic pathogen Pseudomo- nas aeruginosa is capable of colonizing the respiratory tract of individuals with cystic fibrosis (CF), where it undergoes evolution to optimize survival as a persistent chronic human colonizer. The transcriptome of a host-adapted, alginate-overproducing iso- late from a CF patient was determined following growth of the bacteria in the presence of human respiratory mucus. This stable mucoid strain responded to a number of regulatory inputs from the mucus, resulting in an unexpected repression of alginate production. Mucus in the medium also induced the production of catalases and additional peroxide-detoxifying enzymes and caused reorganization of pathways of energy generation. A specific antibacterial type VI secretion system was also induced in mucus-grown cells. Finally, a group of small regulatory RNAs was identified and a fraction of these were mucus regulated. This report provides a snapshot of responses in a pathogen adapted to a human host through assimilation of regulatory signals from tissues, optimizing its long-term survival potential. IMPORTANCE The basis for chronic colonization of patients with cysticfibrosis (CF) by the opportunistic pathogen Pseudomonas aeruginosa continues to represent a challenging problem for basic scientists and clinicians. In this study, the host-adapted, alginate-overproducing Pseudomonas aeruginosa 2192 strain was used to assess the changes in its transcript levels following growth in respiratory CF mucus. Several significant and unexpected discoveries were made: (i) although the alginate overpro- duction in strain 2192 was caused by a stable mutation, a mucus-derived signal caused reduction in the transcript levels of algi- nate biosynthetic genes; (ii) mucus activated the expression of the type VI secretion system, a mechanism for killing of other bac- teria in a mixed population; (iii) expression of a number of genes involved in respiration was altered; and (iv) several small regulatory RNAs were identified, some being mucus regulated. This work highlights the strong influence of the host environ- ment in shaping bacterial survival strategies.