Quinn Robert A, Whiteson Katrine, Lim Yan-Wei, Salamon Peter, Bailey Barbara, Mienardi Simone, Sanchez Savannah E, Blake Don, Conrad Doug, Rohwer Forest
Department of Biology, San Diego State University, San Diego, CA, USA.
Department of Mathematics and Statistics, San Diego State University, San Diego, CA, USA.
ISME J. 2015 Mar 17;9(4):1024-38. doi: 10.1038/ismej.2014.234.
There is a poor understanding of how the physiology of polymicrobial communities in cystic fibrosis (CF) lungs contributes to pulmonary exacerbations and lung function decline. In this study, a microbial culture system based on the principles of the Winogradsky column (WinCF system) was developed to study the physiology of CF microbes. The system used glass capillary tubes filled with artificial sputum medium to mimic a clogged airway bronchiole. Chemical indicators were added to observe microbial physiology within the tubes. Characterization of sputum samples from seven patients showed variation in pH, respiration, biofilm formation and gas production, indicating that the physiology of CF microbial communities varied among patients. Incubation of homogenized tissues from an explant CF lung mirrored responses of a Pseudomonas aeruginosa pure culture, supporting evidence that end-stage lungs are dominated by this pathogen. Longitudinal sputum samples taken through two exacerbation events in a single patient showed that a two-unit drop in pH and a 30% increase in gas production occurred in the tubes prior to exacerbation, which was reversed with antibiotic treatment. Microbial community profiles obtained through amplification and sequencing of the 16S rRNA gene showed that fermentative anaerobes became more abundant during exacerbation and were then reduced during treatment where P. aeruginosa became the dominant bacterium. Results from the WinCF experiments support the model where two functionally different CF microbial communities exist, the persistent Climax Community and the acute Attack Community. Fermentative anaerobes are hypothesized to be the core members of the Attack Community and production of acidic and gaseous products from fermentation may drive developing exacerbations. Treatment targeting the Attack Community may better resolve exacerbations and resulting lung damage.
目前对于囊性纤维化(CF)肺部的多种微生物群落生理学如何导致肺部病情加重和肺功能下降的了解甚少。在本研究中,基于维诺格拉茨基柱原理开发了一种微生物培养系统(WinCF系统),以研究CF微生物的生理学。该系统使用填充有人造痰液培养基的玻璃毛细管来模拟堵塞的气道细支气管。添加化学指示剂以观察管内的微生物生理学。对7名患者的痰液样本进行的表征显示,pH值、呼吸作用、生物膜形成和气体产生存在差异,表明CF微生物群落的生理学在患者之间有所不同。对CF肺外植体的匀浆组织进行培养,其反应与铜绿假单胞菌纯培养物的反应相似,这支持了终末期肺部由该病原体主导的证据。在一名患者中通过两次病情加重事件采集的纵向痰液样本显示,在病情加重之前,管内pH值下降两个单位,气体产生增加30%,抗生素治疗后这种情况得到逆转。通过对16S rRNA基因进行扩增和测序获得的微生物群落图谱显示,发酵厌氧菌在病情加重期间变得更加丰富,然后在治疗期间减少,此时铜绿假单胞菌成为优势菌。WinCF实验的结果支持了这样一种模型,即存在两个功能不同的CF微生物群落,即持续的顶极群落和急性攻击群落。据推测,发酵厌氧菌是攻击群落的核心成员,发酵产生的酸性和气体产物可能会促使病情加重。针对攻击群落的治疗可能能更好地解决病情加重问题以及由此导致的肺损伤。