Evolution of Pseudomonas aeruginosa type III secretion in cystic fibrosis: a paradigm of chronic infection.
Evolution of Pseudomonas aeruginosa type III secretion in cystic fibrosis: a paradigm of chronic infection.
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DOI：
10.1016/j.trsl.2008.10.003
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发表时间：
2008-12
期刊：
影响因子：
--
通讯作者：
Hauser AR
中科院分区：
文献类型：
--
作者：
Jain M;Bar-Meir M;McColley S;Cullina J;Potter E;Powers C;Prickett M;Seshadri R;Jovanovic B;Petrocheilou A;King JD;Hauser AR
Pseudomonas aeruginosa (PA) from acute and chronic (e.g. cystic fibrosis [CF]) infections differ in several respects though they can worsen prognosis in each context. Factors that facilitate conversion from an acute to chronic phenotype are poorly understood. Type III (T3) secretion proteins are virulence factors associated with poorer outcomes in acute infections, but little is known about their role in CF. We wished to characterize T3 secretion in CF PA isolates and examine its role in clinical outcomes. One-hundred fourteen CF subjects were divided into 3 cohorts: 1st infected individuals, chronically infected (CI) children, and adults. Serial respiratory cultures were analyzed for T3 secretion. Serial spirometry and exacerbation data were prospectively collected. In 1st infection, 45.2% +/− 9.1% of PA isolates secreted T3 proteins compared to 29.1% +/− 4.2% and 11.5% +/− 3.0% in CI children and CI adults, respectively (p<0.001). There was an inverse correlation between duration of PA infection and percent T3 positive isolates (r=−0.32, p<0.001). Overall there was no association between T3 secretion and pulmonary outcomes, but in the subgroup of subjects who had at least one T3 positive organism, T3 secretion was inversely correlated with FEV1 decline (r=−0.35, p=0.02). In 1st infection, 82% of cultures grew either all or no T3 positive organisms. In these patients, T3 secretion was associated with greater risk of subsequent PA isolation (p<0.001). In CF, PA T3 secretion decreases with residence time in lung, may predict FEV1 decline in patients who have detectable T3 organisms, and may facilitate persistence following 1st infection.
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