Biogeochemical forces shape the composition and physiology of polymicrobial communities in the cystic fibrosis lung.
Biogeochemical forces shape the composition and physiology of polymicrobial communities in the cystic fibrosis lung.
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DOI：
10.1128/mbio.00956-13
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发表时间：
2014-03-18
期刊：
影响因子：
6.4
通讯作者：
Whiteson KL
中科院分区：
文献类型：
--
作者：
Quinn RA;Lim YW;Maughan H;Conrad D;Rohwer F;Whiteson KL
囊性纤维化（CF）肺含有厚粘液，这些粘液由适应CF肺环境数十年的机会性病原体定殖。与采样气道相关的困难阻碍了对这些病原体所暴露的生化微生境的彻底检查。一种间接的方法是研究微生物群落对这些微生境的反应，通过对痰液样本中的微生物DNA和RNA进行高通量测序来促进。对来自多个CF患者的微生物宏基因组和元转录组进行测序，并且通过与NCBI和京都基因和基因组百科全书（KEGG）数据库层级的序列同源性对读段进行分类和功能分配。为了进行比较，还分析了来自人类微生物组计划（HMP）的唾液微生物宏基因组。这些分析鉴定了CF微生物编码和表达的功能显著富集氨基酸催化剂、叶酸生物合成和硫辛酸生物合成。数据表明，该社区使用氧化磷酸化作为主要的能源，但终端电子受体是不同的。硝酸盐还原是最丰富的厌氧呼吸途径，硝酸盐还原酶基因主要分配给假单胞菌和罗氏菌。虽然氮循环中存在许多还原途径，但由于氧化途径的缺失，氮循环是不完整的。由于CF微生物群落富含氨基酸催化剂和不完全的氮循环，CF微生物群落表现为积累氨。使用CF细支气管培养模型系统实验验证了这一发现。数据还揭示了丰富的传感和运输铁，铵，锌，和其他金属沿着低氧环境。这项研究揭示了CF微生物组的核心生物化学和生理学。囊性纤维化（CF）微生物群落是复杂的，并且在CF患者的一生中适应肺的环境条件。该分析说明了CF微生物群落在CF肺生物化学背景下的核心功能。有许多关于CF肺内单个微生物的代谢和生理学的研究，但没有一项研究能够共同分析整个微生物组的数据。了解栖息在CF肺中的微生物的核心代谢可以为新型疗法提供新的靶点。CF病原体生存所依赖的基本过程可能是该病原体群落的致命弱点。旨在破坏CF微生物群落未充分研究的生存策略的新疗法可能会成功对抗其他无法治疗或耐药的微生物。
The cystic fibrosis (CF) lung contains thick mucus colonized by opportunistic pathogens which adapt to the CF lung environment over decades. The difficulty associated with sampling airways has impeded a thorough examination of the biochemical microhabitats these pathogens are exposed to. An indirect approach is to study the responses of microbial communities to these microhabitats, facilitated by high-throughput sequencing of microbial DNA and RNA from sputum samples. Microbial metagenomes and metatranscriptomes were sequenced from multiple CF patients, and the reads were assigned taxonomy and function through sequence homology to NCBI and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database hierarchies. For a comparison, saliva microbial metagenomes from the Human Microbiome Project (HMP) were also analyzed. These analyses identified that functions encoded and expressed by CF microbes were significantly enriched for amino acid catabolism, folate biosynthesis, and lipoic acid biosynthesis. The data indicate that the community uses oxidative phosphorylation as a major energy source but that terminal electron acceptors were diverse. Nitrate reduction was the most abundant anaerobic respiratory pathway, and genes for nitrate reductase were largely assigned to Pseudomonas and Rothia. Although many reductive pathways of the nitrogen cycle were present, the cycle was incomplete, because the oxidative pathways were absent. Due to the abundant amino acid catabolism and incomplete nitrogen cycle, the CF microbial community appears to accumulate ammonia. This finding was verified experimentally using a CF bronchiole culture model system. The data also revealed abundant sensing and transport of iron, ammonium, zinc, and other metals along with a low-oxygen environment. This study reveals the core biochemistry and physiology of the CF microbiome. The cystic fibrosis (CF) microbial community is complex and adapts to the environmental conditions of the lung over the lifetime of a CF patient. This analysis illustrates the core functions of the CF microbial community in the context of CF lung biochemistry. There are many studies of the metabolism and physiology of individual microbes within the CF lung, but none that collectively analyze data from the whole microbiome. Understanding the core metabolism of microbes that inhabit the CF lung can provide new targets for novel therapies. The fundamental processes that CF pathogens rely on for survival may represent an Achilles heel for this pathogenic community. Novel therapies that are designed to disrupt understudied survival strategies of the CF microbial community may succeed against otherwise untreatable or antibiotic-resistant microbes.