Department of Biological and Environmental Engineering, Cornell University, Ithaca, NY 14853, USA.
1] Department of Biological and Environmental Engineering, Cornell University, Ithaca, NY 14853, USA [2] iAMB - Institute of Applied Microbiology, RWTH Aachen University, Aachen, Germany.
ISME J. 2014 Jun;8(6):1210-20. doi: 10.1038/ismej.2013.232. Epub 2014 Jan 9.
The respiratory tract of cystic fibrosis (CF) patients harbor persistent microbial communities (CF airway microbiome) with Pseudomonas aeruginosa emerging as a dominant pathogen. Within a polymicrobial infection, interactions between co-habitant microbes can be important for pathogenesis, but even when considered, these interactions are not well understood. Here, we show with in vitro experiments that, compared with glucose, common fermentation products from co-habitant bacteria significantly increase virulence factor production, antimicrobial activity and biofilm formation of P. aeruginosa. The maximum stimulating effect was produced with the fermentation product 2,3-butanediol, which is a substrate for P. aeruginosa, resulting in a metabolic relationship between fermenters and this pathogen. The global transcription regulator LasI LasR, which controls quorum sensing, was upregulated threefold with 2,3-butanediol, resulting in higher phenazine and exotoxin concentrations and improved biofilm formation. This indicates that the success of P. aeruginosa in CF airway microbiomes could be governed by the location within the food web with fermenting bacteria. Our findings suggest that interbacterial metabolite transfer in polymicrobial infections stimulates virulence of P. aeruginosa and could have a considerable impact on disease progression.
囊性纤维化 (CF) 患者的呼吸道中存在持续存在的微生物群落（CF 气道微生物组），铜绿假单胞菌是主要的病原体。在多微生物感染中，共生微生物之间的相互作用对于发病机制可能很重要，但即使考虑到这一点，这些相互作用也尚未得到很好的理解。在这里，我们通过体外实验表明，与葡萄糖相比，共生细菌的常见发酵产物可显著增加铜绿假单胞菌毒力因子的产生、抗菌活性和生物膜形成。发酵产物 2,3-丁二醇产生的刺激作用最大，它是铜绿假单胞菌的底物，导致发酵剂和这种病原体之间存在代谢关系。控制群体感应的全局转录调节剂 LasI LasR 上调了三倍，导致吩嗪和外毒素浓度更高，生物膜形成更好。这表明，铜绿假单胞菌在 CF 气道微生物组中的成功可能受到其在食物网中位置的控制，发酵细菌就在其中。我们的研究结果表明，多微生物感染中的细菌间代谢产物转移可刺激铜绿假单胞菌的毒力，这可能对疾病进展产生重大影响。
