AJRCMB：吩嗪化合物损伤囊性纤维化病人的肺部功能

近日，来自加州理工大学的研究者通过研究发现，囊性纤维化病人呼吸道中吩嗪化合物的存在可以对患者肺功能以及肺部微生物复杂多样性产生负面影响，相关研究成果刊登在了国际著名杂志American Journal of Respiratory Cell and Molecular Biology上。

目前科学家进行了大量的体外研究，也揭示了许多毒力因子是如何影响致病菌以及宿主组织结构的。但是在体内研究却相对较少。因此在本项研究中，研究者测定了肺部囊性纤维化病人呼吸道中细菌产生的吩嗪化合物的平衡。

吩嗪化合物是一种由绿脓杆菌产生的一种氧化还原小分子化合物，细菌在生长过程中可以产生吩嗪化合物来破坏宿主的组织功能。而且在与其它细菌的“争夺”中，绿脓杆菌也可以通过分泌绿脓菌素来抑制其它细菌的生长，从而里争夺“领地”，吩嗪在细菌生长过程中扮演着重要的角色。

在本文中，研究者对患者痰液中的吩嗪进行了定量测定，用以指示细菌的感染状态以及生长状态，从而来评估囊性纤维化病人肺部微生物群落的广谱效用。研究揭示了吩嗪化合物绿脓菌素和吩嗪1羧酸（PCA）对肺部功能有负向影响。而且在肺功能严重下降的患者体内也发现了较高水平的吩嗪产量。

研究者同时也指出，吩嗪的浓度对于肺部乃至呼吸道中的微生物群落多样性也有不利影响，研究者Dianne K Newman表示，这些研究数据揭示了吩嗪和囊性纤维化病人的肺部功能负向相关，而且体内的环境测量指数更有利于预测疾病的感染情况，以及便于制定出更为合理的治疗策略。

doi:10.1165/rcmb.2012-0088OC
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Phenazine Content in the Cystic Fibrosis Respiratory Tract Negatively Correlates with Lung Function and Microbial Complexity

Ryan C Hunter1, Vanja Klepac-Ceraj2, Magen M Lorenzi3, Hannah Grotzinger4, Thomas R Martin5 and Dianne K Newman6⇓

While 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 towards characterizing the chemistry of infected environments, we measured phenazine abundance in the lungs of cystic fibrosis patients. 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 for the cells that produce them. Here, we quantify phenazines within expectorated sputum, characterize the P. aeruginosa populations responsible for phenazine production, and assess their broad effects on the CF lung microflora. Chemical analysis of expectorated sputum showed that the concentrations of two phenazines - pyocyanin (PYO) and phenazine-1-carboxylic acid (PCA) - negatively correlate (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 rate of decline. The constituent P. aeruginosa populations within each patient showed diverse phenazine production capacity: early in infection, individual isolates produced more PYO than later in 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 negatively correlated with phenazine concentrations and lung function decline, 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.