期刊
MICROORGANISMS
卷 10, 期 4, 页码 -出版社
MDPI
DOI: 10.3390/microorganisms10040716
关键词
chemotaxis; bile; Pseudomonas aeruginosa; cystic fibrosis; bronchial epithelial cells
类别
资金
- US Cystic Fibrosis Foundation [HILL17P0]
- NIH
- CF Foundation [STANTO19R0, R01 HL151385-01A]
Cystic fibrosis is a life-threatening multi-organ disease characterized by susceptibility to chronic pulmonary infections. Bile is believed to contribute to the colonization and pathogenesis of Pseudomonas aeruginosa in the lung.
Cystic fibrosis (CF) is a life-threatening, inherited, multi-organ disease that renders patients susceptible throughout their lives to chronic and ultimately deteriorating protracted pulmonary infections. Those infections are dominated in adulthood by the opportunistic pathogen, Pseudomonas aeruginosa (Pa). As with other advancing respiratory illnesses, people with CF (pwCF) also frequently suffer from gastroesophageal reflux disease (GERD), including bile aspiration into the lung. GERD is a major co-morbidity factor in pwCF, with a reported prevalence of 35-81% in affected individuals. Bile is associated with the early acquisition of Pa in CF patients and in vitro studies show that it causes Pa to adopt a chronic lifestyle. We hypothesized that Pa is chemoattracted to bile in the lung environment. To evaluate, we developed a novel chemotaxis experimental system mimicking the lung environment using CF-derived bronchial epithelial (CFBE) cells which allowed for the evaluation of Pa (strain PAO1) chemotaxis in a physiological scenario superior to the standard in vitro systems. We performed qualitative and quantitative chemotaxis tests using this new experimental system, and microcapillary assays to demonstrate that bovine bile is a chemoattractant for Pa and is positively correlated with bile concentration. These results further buttress the hypothesis that bile likely contributes to the colonization and pathogenesis of Pa in the lung, particularly in pwCF.
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