Evidence and Role for Bacterial Mucin Degradation in Cystic Fibrosis Airway Disease
Evidence and Role for Bacterial Mucin Degradation in Cystic Fibrosis Airway Disease
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DOI：
10.1371/journal.ppat.1005846
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发表时间：
2016-08-01
期刊：
影响因子：
6.7
通讯作者：
Hunter, Ryan C.
中科院分区：
文献类型：
--
作者：
Flynn, Jeffrey M.;Niccum, David;Hunter, Ryan C.
囊性纤维化（CF）患者的慢性肺部感染由复杂的微生物群落组成，这些微生物群落会引起持续性炎症和气道损伤。尽管在下呼吸道定植的细菌密度很高，但维持细菌体内生长的营养源以及这些营养素是如何获得的还没有很好地表征。在这项研究中，我们研究了粘蛋白作为CF肺微生物群重要碳库的可能性。虽然铜绿假单胞菌不能有效地利用粘蛋白分离，我们发现，厌氧，粘蛋白发酵细菌可以刺激CF病原体的强劲增长时，提供完整的粘蛋白作为唯一的碳源。16S rRNA测序和痰液富集培养也证实CF患者气道中普遍存在降解粘蛋白的厌氧菌。这些粘蛋白降解社区在体外的集体发酵代谢产生的氨基酸和短链脂肪酸（丙酸酯和乙酸酯）在粘蛋白的生长过程中，相同的代谢产物也被发现在痰液中丰富。这些发现的意义得到了体内铜绿假单胞菌基因表达的支持，其揭示了丙酸盐催化所需的基因表达的提高。鉴于丙酸盐完全来自细菌发酵，这些数据为粘蛋白发酵细菌在下呼吸道的碳通量中的重要作用提供了证据。更具体地，通常定义为微生物的微生物可能通过降解粘蛋白而导致气道疾病，进而为病原体提供营养，否则无法有效地获得肺中的碳。
Chronic lung infections in cystic fibrosis (CF) patients are composed of complex microbial communities that incite persistent inflammation and airway damage. Despite the high density of bacteria that colonize the lower airways, nutrient sources that sustain bacterial growth in vivo, and how those nutrients are derived, are not well characterized. In this study, we examined the possibility that mucins serve as an important carbon reservoir for the CF lung microbiota. While Pseudomonas aeruginosa was unable to efficiently utilize mucins in isolation, we found that anaerobic, mucin-fermenting bacteria could stimulate the robust growth of CF pathogens when provided intact mucins as a sole carbon source. 16S rRNA sequencing and enrichment culturing of sputum also identified that mucin-degrading anaerobes are ubiquitous in the airways of CF patients. The collective fermentative metabolism of these mucin-degrading communities in vitro generated amino acids and short chain fatty acids (propionate and acetate) during growth on mucin, and the same metabolites were also found in abundance within expectorated sputum. The significance of these findings was supported by in vivo P. aeruginosa gene expression, which revealed a heightened expression of genes required for the catabolism of propionate. Given that propionate is exclusively derived from bacterial fermentation, these data provide evidence for an important role of mucin fermenting bacteria in the carbon flux of the lower airways. More specifically, microorganisms typically defined as commensals may contribute to airway disease by degrading mucins, in turn providing nutrients for pathogens otherwise unable to efficiently obtain carbon in the lung.