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A novel mechanism for the biogenesis of outer membrane vesicles in Gram-negative bacteria.
Nature Communications ( IF 14.7 ) Pub Date : 2016-Jan-25 , DOI: 10.1038/ncomms10515
Sandro Roier 1 , Franz G Zingl 1 , Fatih Cakar 1 , Sanel Durakovic 1 , Paul Kohl 1 , Thomas O Eichmann 1 , Lisa Klug 2 , Bernhard Gadermaier 1 , Katharina Weinzerl 1 , Ruth Prassl 3 , Achim Lass 1 , Günther Daum 2 , Joachim Reidl 1 , Mario F Feldman 4 , Stefan Schild 1
Affiliation  

Bacterial outer membrane vesicles (OMVs) have important biological roles in pathogenesis and intercellular interactions, but a general mechanism of OMV formation is lacking. Here we show that the VacJ/Yrb ABC (ATP-binding cassette) transport system, a proposed phospholipid transporter, is involved in OMV formation. Deletion or repression of VacJ/Yrb increases OMV production in two distantly related Gram-negative bacteria, Haemophilus influenzae and Vibrio cholerae. Lipidome analyses demonstrate that OMVs from VacJ/Yrb-defective mutants in H. influenzae are enriched in phospholipids and certain fatty acids. Furthermore, we demonstrate that OMV production and regulation of the VacJ/Yrb ABC transport system respond to iron starvation. Our results suggest a new general mechanism of OMV biogenesis based on phospholipid accumulation in the outer leaflet of the outer membrane. This mechanism is highly conserved among Gram-negative bacteria, provides a means for regulation, can account for OMV formation under all growth conditions, and might have important pathophysiological roles in vivo.

中文翻译:

革兰氏阴性菌外膜囊泡生物发生的新机制。

细菌外膜囊泡 (OMV) 在发病机制和细胞间相互作用中具有重要的生物学作用,但缺乏 OMV 形成的一般机制。在这里,我们显示 VacJ/Yrb ABC(ATP 结合盒)运输系统,一种建议的磷脂转运蛋白,参与 OMV 的形成。VacJ/Yrb 的缺失或抑制会增加两种远缘革兰氏阴性菌(流感嗜血杆菌和霍乱弧菌)中 OMV 的产生。脂质组分析表明,来自流感嗜血杆菌中 VacJ/Yrb 缺陷突变体的 OMV 富含磷脂和某些脂肪酸。此外,我们证明了 VacJ/Yrb ABC 运输系统的 OMV 生产和调节对铁饥饿有反应。我们的研究结果表明基于外膜外叶磷脂积累的 OMV 生物发生的新一般机制。这种机制在革兰氏阴性细菌中高度保守,提供了一种调节手段,可以解释所有生长条件下的 OMV 形成,并且可能在体内具有重要的病理生理学作用。
更新日期:2016-01-28
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