A probiotic yeast-based immunotherapy against Clostridioides difficile infection.
A probiotic yeast-based immunotherapy against Clostridioides difficile infection.
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DOI：
10.1126/scitranslmed.aax4905
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发表时间：
2020-10-28
影响因子：
17.1
通讯作者：
Feng H
中科院分区：
文献类型：
--
作者：
Chen K;Zhu Y;Zhang Y;Hamza T;Yu H;Saint Fleur A;Galen J;Yang Z;Feng H
抗生素耐药性艰难梭菌是一种厌氧革兰氏阳性细菌，定植于结肠，每年在美国造成29，000多人死亡。因此，C.艰难梭菌感染（CDI）对公众健康构成了紧迫的威胁。抗体介导的TcdA和TcdB毒素（CDI的主要毒力因子）的中和代表了在不引起抗生素耐药性的情况下对抗疾病的有效策略。然而，目前的抗毒素方法大多基于单克隆抗体的肠胃外输注，其昂贵、窄谱并且针对肠道疾病不是最佳的。在这里，我们设计了益生菌布拉酵母，使其组成性分泌一种单一的四特异性抗体，该抗体有效且广泛地中和两种毒素，并在预防性和治疗性小鼠疾病模型中证明了对原发性和复发性CDI的保护作用。这种酵母免疫疗法是口服给药的，可以与抗生素同时使用，并且可能具有预防CDI风险和治疗CDI患者的潜力。
Antibiotic-resistant Clostridioides difficile is an anaerobic Gram-positive bacterium that colonizes the colon and is responsible for more than 29,000 deaths in the United States each year. Hence, C. difficile infection (CDI) poses an urgent threat to public health. Antibody-mediated neutralization of TcdA and TcdB toxins, the major virulence factors of CDI, represents an effective strategy to combat the disease without invoking antibiotic resistance. However, current antitoxin approaches are mostly based on parenteral infusion of monoclonal antibodies that are costly, narrow spectrum, and not optimized against the intestinal disease. Here, we engineered probiotic Saccharomyces boulardii to constitutively secrete a single tetra-specific antibody that potently and broadly neutralized both toxins and demonstrated protection against primary and recurrent CDI in both prophylactic and therapeutic mouse models of disease. This yeast immunotherapy is orally administered, can be used concurrently with antibiotics, and may have potential as a prophylactic against CDI risk and as a therapeutic for patients with CDI.
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影响因子：
4.2
作者：
Chow SK;Casadevall A
通讯作者：
Casadevall A
影响因子：
14.8
作者：
Gietz, R. Daniel;Schiestl, Robert H.
通讯作者：
Schiestl, Robert H.
影响因子：
4.9
作者：
Douradinha, Bruno;Reis, Viviane C. B.;Marques, Ernesto T. A., Jr.
通讯作者：
Marques, Ernesto T. A., Jr.
影响因子：
--
作者：
Davies, Nicola L.;Compson, Joanne E.;Humphreys, David P.
通讯作者：
Humphreys, David P.
影响因子：
3.1
作者：
Castagliuolo, I;Riegler, MF;Pothoulakis, C
通讯作者：
Pothoulakis, C