Ecological Succession of Polymicrobial Communities in the Cystic Fibrosis Airways.
Ecological Succession of Polymicrobial Communities in the Cystic Fibrosis Airways.
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DOI：
10.1128/msystems.00809-20
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发表时间：
2020-12-01
期刊：
影响因子：
6.4
通讯作者：
Guttman DS
中科院分区：
文献类型：
--
作者：
Khanolkar RA;Clark ST;Wang PW;Hwang DM;Yau YCW;Waters VJ;Guttman DS
针对囊性纤维化（CF）肺部感染的抗菌治疗主要针对传统的、研究充分的CF病原体，如铜绿假单胞菌和洋葱伯克霍尔德氏菌复合体，尽管CF肺部含有复杂且动态的多微生物群落。临床上对主要病原体的关注忽视了疾病病理学中潜在的重要社区水平的相互作用，这也许可以解释为什么这些治疗往往不如基于体外测试的预测有效。针对囊性纤维化（CF）肺部感染的抗菌治疗主要针对传统的、研究充分的CF病原体，如铜绿假单胞菌和洋葱伯克霍尔德氏菌复合体，尽管CF肺部含有复杂且动态的多微生物群落。临床上对主要病原体的关注忽视了疾病病理学中潜在的重要社区水平的相互作用，这也许可以解释为什么这些治疗往往不如基于体外测试的预测有效。更好地了解这个生态系统的生态动态，可以使临床医生利用这些相互作用，从而改善治疗效果。与所有生态系统一样，CF肺微生物群落通过一系列阶段发展，每个阶段可能存在不同的微生物群落，这些微生物群落产生独特的宿主-微生物和微生物-微生物相互作用、代谢谱和临床表型。虽然已经开发了一些有见地的模型来解释这些阶段和相互作用，但没有统一的模型来描述这些感染如何发展和持续。在这里，我们回顾了CF气道生态学的当前观点，并提出了CF生态演替（CFES）模型，该模型旨在捕捉CF肺部感染的空间和时间复杂性，解决当前疾病管理的挑战，并为生态驱动的治疗策略的发展提供信息。
Antimicrobial therapies against cystic fibrosis (CF) lung infections are largely aimed at the traditional, well-studied CF pathogens such as Pseudomonas aeruginosa and Burkholderia cepacia complex, despite the fact that the CF lung harbors a complex and dynamic polymicrobial community. A clinical focus on the dominant pathogens ignores potentially important community-level interactions in disease pathology, perhaps explaining why these treatments are often less effective than predicted based on in vitro testing. Antimicrobial therapies against cystic fibrosis (CF) lung infections are largely aimed at the traditional, well-studied CF pathogens such as Pseudomonas aeruginosa and Burkholderia cepacia complex, despite the fact that the CF lung harbors a complex and dynamic polymicrobial community. A clinical focus on the dominant pathogens ignores potentially important community-level interactions in disease pathology, perhaps explaining why these treatments are often less effective than predicted based on in vitro testing. A better understanding of the ecological dynamics of this ecosystem may enable clinicians to harness these interactions and thereby improve treatment outcomes. Like all ecosystems, the CF lung microbial community develops through a series of stages, each of which may present with distinct microbial communities that generate unique host-microbe and microbe-microbe interactions, metabolic profiles, and clinical phenotypes. While insightful models have been developed to explain some of these stages and interactions, there is no unifying model to describe how these infections develop and persist. Here, we review current perspectives on the ecology of the CF airway and present the CF Ecological Succession (CFES) model that aims to capture the spatial and temporal complexity of CF lung infection, address current challenges in disease management, and inform the development of ecologically driven therapeutic strategies.