Harnessing hypoxia: bacterial adaptation and chronic infection in cystic fibrosis.

Abstract

The exquisite ability of bacteria to adapt to their environment is essential for their capacity to colonize hostile niches. In the cystic fibrosis (CF) lung, hypoxia is among several environmental stresses that opportunistic pathogens must overcome to persist and chronically colonize. Although the role of hypoxia in the host has been widely reviewed, the impact of hypoxia on bacterial pathogens has not yet been studied extensively. This review considers the bacterial oxygen-sensing mechanisms in three species that effectively colonize the lungs of people with CF, namely Pseudomonas aeruginosa, Burkholderia cepacia complex, and Mycobacterium abscessus and draws parallels between their three proposed oxygen-sensing two-component systems: BfiSR, FixLJ, and DosRS, respectively. Moreover, each species expresses regulons that respond to hypoxia: Anr, Lxa, and DosR, and encode multiple proteins that share similar homologies and function. Many adaptations that these pathogens undergo during chronic infection, including antibiotic resistance, protease expression, or changes in motility, have parallels in the responses of the respective species to hypoxia. It is likely that exposure to hypoxia in their environmental habitats predispose these pathogens to colonization of hypoxic niches, arming them with mechanisms than enable their evasion of the immune system and establish chronic infections. Overcoming hypoxia presents a new target for therapeutic options against chronic lung infections.