Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, USA; Marsico Lung Institute, University of North Carolina, Chapel Hill, NC, USA.
Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, USA; Marsico Lung Institute, University of North Carolina, Chapel Hill, NC, USA.
Curr Opin Pharmacol. 2022 Aug;65:102262. doi: 10.1016/j.coph.2022.102262. Epub 2022 Jul 2.
This review guides the reader through the current understanding of the dynamic changes that occur within the cystic fibrosis (CF) lung that allow Pseudomonas aeruginosa to become the dominant pathogen associated with CF. Although recent studies provide some insight, the mechanisms that drive the changing landscape of the lung environment throughout an individual's lifetime that prime P. aeruginosa to take over and establish chronic infection within the lungs, remain poorly understood. We explore how the CF lung environment shapes the ability of P. aeruginosa to persist in spite of intense antimicrobial therapy. We also highlight the pioneering use of a triple combination cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy, Trikafta, to restore CFTR function and how it influences P. aeruginosa persistence in the CF lung. We utilize existing data for single modulator therapies to extrapolate the potential future of pathogen infection in the era of Trikafta therapy.
这篇综述引导读者了解囊性纤维化 (CF) 肺部内发生的动态变化，这些变化使铜绿假单胞菌成为与 CF 相关的主要病原体。尽管最近的研究提供了一些见解，但驱动个体一生中肺部环境不断变化的机制，使铜绿假单胞菌得以接管并在肺部建立慢性感染，仍知之甚少。我们探讨了 CF 肺部环境如何塑造铜绿假单胞菌在尽管进行了强烈的抗菌治疗仍能持续存在的能力。我们还强调了开创性地使用三联囊性纤维化跨膜电导调节剂 (CFTR) 调节剂治疗，Trikafta，来恢复 CFTR 功能，以及它如何影响 CF 肺部中铜绿假单胞菌的持续存在。我们利用单调节剂治疗的现有数据来推断在 Trikafta 治疗时代病原体感染的潜在未来。
