Division of Biological Sciences, California Institute of Technology, Pasadena, CA 91125, USA.
Am J Respir Cell Mol Biol. 2012 Dec;47(6):738-45. doi: 10.1165/rcmb.2012-0088OC. Epub 2012 Aug 3.
Although much is known about how virulence factors affect pathogens and host tissues in vitro, far less is understood about their dynamics in vivo. As a step toward characterizing the chemistry of infected environments, we measured phenazine abundance in the lungs of patients with cystic fibrosis (CF). Phenazines are redox-active small molecules produced by Pseudomonas aeruginosa that damage host epithelia, curb the growth of competing organisms, and play physiologically important roles in the cells that produce them. Here, we quantify phenazines within expectorated sputum, characterize the P. aeruginosa populations responsible for phenazine production, and assess their relationship to CF lung microflora. Chemical analyses of expectorated sputum showed that the concentrations of two phenazines, namely, pyocyanin (PYO) and phenazine-1-carboxylic acid (PCA), were negatively correlated (ρ = -0.68 and -0.57, respectively) with lung function. Furthermore, the highest phenazine concentrations were found in patients whose pulmonary function showed the greatest rates of decline. The constituent P. aeruginosa populations within each patient showed diverse capacities for phenazine production. Early during infection, individual isolates produced more PYO than later during infection. However, total PYO concentrations in sputum at any given stage correlated well with the average production by the total P. aeruginosa population. Finally, bacterial community complexity was negatively correlated with phenazine concentrations and declines in lung function, suggesting a link to the refinement of the overall microbial population. Together, these data demonstrate that phenazines negatively correlate with CF disease states in ways that were previously unknown, and underscore the importance of defining in vivo environmental parameters to better predict clinical outcomes of infections.
虽然人们已经了解了很多关于毒力因子在体外如何影响病原体和宿主组织的知识，但对于它们在体内的动态变化却知之甚少。为了深入了解感染环境的化学特性，我们测量了囊性纤维化（CF）患者肺部中吩嗪的含量。吩嗪是铜绿假单胞菌产生的具有氧化还原活性的小分子，会损伤宿主上皮细胞，抑制竞争生物的生长，并在产生它们的细胞中发挥重要的生理作用。在这里，我们定量了咳出的痰中的吩嗪，描述了产生吩嗪的铜绿假单胞菌种群，并评估了它们与 CF 肺部微生物群的关系。对咳出的痰进行化学分析表明，两种吩嗪，即绿脓菌素（PYO）和吩嗪-1-羧酸（PCA）的浓度与肺功能呈负相关（ρ分别为-0.68 和-0.57）。此外，在肺功能下降最快的患者中，吩嗪的浓度最高。每个患者体内的铜绿假单胞菌种群在产生吩嗪方面表现出不同的能力。在感染早期，单个分离株产生的 PYO 多于感染后期。然而，在任何特定阶段痰中的总 PYO 浓度与铜绿假单胞菌总种群的平均产量很好地相关。最后，细菌群落的复杂性与吩嗪浓度和肺功能下降呈负相关，这表明与整体微生物种群的细化有关。总之，这些数据表明，吩嗪与 CF 疾病状态呈负相关，这是以前未知的，强调了定义体内环境参数以更好地预测感染临床结果的重要性。
