A bacterial endosymbiont of the fungus Rhizopus microsporus drives phagocyte evasion and opportunistic virulence.
A bacterial endosymbiont of the fungus Rhizopus microsporus drives phagocyte evasion and opportunistic virulence.
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DOI：
10.1016/j.cub.2022.01.028
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发表时间：
2022-03-14
期刊：
影响因子：
--
通讯作者：
Voelz K
中科院分区：
文献类型：
--
作者：
Itabangi H;Sephton-Clark PCS;Tamayo DP;Zhou X;Starling GP;Mahamoud Z;Insua I;Probert M;Correia J;Moynihan PJ;Gebremariam T;Gu Y;Ibrahim AS;Brown GD;King JS;Ballou ER;Voelz K
由环境真菌引起的机会性感染是一个日益严重的临床问题，其驱动因素是免疫功能低下人群的增加。Mucorales目的孢子在环境中无处不在，但也可以通过萌发和逃避哺乳动物宿主免疫系统引起人类急性侵袭性感染。它们是如何做到这一点的，以及获得毒力机制的进化驱动因素尚不清楚。在这里，我们展示了临床分离的小孢子根霉含有斑马鱼和小鼠毒力所需的皮氏Ralstonia细菌内共生体，并且这种内共生体能够分泌有效抑制土壤变形虫Dictyostelium disideum生长的因子，以及它们吞噬和杀死其他微生物的能力。由于变形虫是细菌和真菌的天然环境捕食者，我们认为这种三界相互作用有助于建立内共生关系和获得抗吞噬细胞活性。重要的是，我们发现这种活性还可以保护真菌孢子免受人类巨噬细胞的吞噬和清除，并且去除内共生体使真菌孢子在体内无毒。总之，这些发现描述了细菌内共生体在动物小孢子根霉发病机制中的新作用，并提出了通过与阿米巴虫的环境相互作用获得毒力的机制。细菌内共生体保护真菌孢子免受吞噬细胞的侵袭一种分泌因子阻断环境变形虫的生长和杀伤内共生体提高真菌的抗逆性内共生体还允许逃避脊椎动物免疫细胞和体内毒力环境真菌如何进化出毒力机制从而机会性地感染人类尚不清楚。Itabangi等人发现了一种三界相互作用，即生活在真菌内的细菌内共生体导致分泌因子的产生，该因子阻断阿米巴虫的捕食活动，并在动物模型中驱动毒力。
Opportunistic infections by environmental fungi are a growing clinical problem, driven by an increasing population of people with immunocompromising conditions. Spores of the Mucorales order are ubiquitous in the environment but can also cause acute invasive infections in humans through germination and evasion of the mammalian host immune system. How they achieve this and the evolutionary drivers underlying the acquisition of virulence mechanisms are poorly understood. Here, we show that a clinical isolate of Rhizopus microsporus contains a Ralstonia pickettii bacterial endosymbiont required for virulence in both zebrafish and mice and that this endosymbiosis enables the secretion of factors that potently suppress growth of the soil amoeba Dictyostelium discoideum, as well as their ability to engulf and kill other microbes. As amoebas are natural environmental predators of both bacteria and fungi, we propose that this tri-kingdom interaction contributes to establishing endosymbiosis and the acquisition of anti-phagocyte activity. Importantly, we show that this activity also protects fungal spores from phagocytosis and clearance by human macrophages, and endosymbiont removal renders the fungal spores avirulent in vivo. Together, these findings describe a new role for a bacterial endosymbiont in Rhizopus microsporus pathogenesis in animals and suggest a mechanism of virulence acquisition through environmental interactions with amoebas. Bacterial endosymbionts protect fungal spores from phagocytes A secreted factor blocks growth and killing by environmental amoebas Endosymbionts improve fungal stress resistance Endosymbiosis also allows the evasion of vertebrate immune cells and virulence in vivo How environmental fungi evolved virulence mechanisms to opportunistically infect humans is unclear. Itabangi et al. identify a tri-kingdom interaction, whereby a bacterial endosymbiont living within a fungus causes the generation of a secreted factor that blocks the predatory activity of amoebas and drives virulence in animal models.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
3.7
作者：
Chamilos G;Ganguly D;Lande R;Gregorio J;Meller S;Goldman WE;Gilliet M;Kontoyiannis DP
通讯作者：
Kontoyiannis DP
DOI：
10.4049/jimmunol.1300748
发表时间：
2013-09-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Carrion Sde J;Leal SM Jr;Ghannoum MA;Aimanianda V;Latgé JP;Pearlman E
通讯作者：
Pearlman E
DOI：
10.1073/pnas.2110669118
发表时间：
2021-09-14
影响因子：
11.1
作者：
Büttner H;Niehs SP;Vandelannoote K;Cseresnyés Z;Dose B;Richter I;Gerst R;Figge MT;Stinear TP;Pidot SJ;Hertweck C
通讯作者：
Hertweck C
影响因子：
28.3
作者：
Ballou ER;Avelar GM;Childers DS;Mackie J;Bain JM;Wagener J;Kastora SL;Panea MD;Hardison SE;Walker LA;Erwig LP;Munro CA;Gow NA;Brown GD;MacCallum DM;Brown AJ
通讯作者：
Brown AJ