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利用斑马鱼胚胎评估鲍曼不动杆菌的毒力和噬菌体治疗效果。

Assessing Acinetobacter baumannii virulence and treatment with a bacteriophage using zebrafish embryos.

机构信息

International Iberian Nanotechnology Laboratory (INL), Braga, Portugal.

CEB-Center of Biological Engineering, University of Minho, Braga, Portugal.

出版信息

FASEB J. 2023 Jul;37(7):e23013. doi: 10.1096/fj.202300385R.

Abstract

Acinetobacter baumannii is the leading bacteria causative of nosocomial infections, with high fatality rates, mostly due to their multi-resistance to antibiotics. The capsular polysaccharide (k-type) is a major virulence factor. Bacteriophages are viruses that specifically infect bacteria and have been used to control drug-resistant bacterial pathogens. In particular, A. baumannii phages can recognize specific capsules, from a diversity of >125 that exist. This high specificity demands the in vivo identification of the most virulent A. baumannii k-types that need to be targeted by phage therapy. Currently, the zebrafish embryo has particularly attained interest for in vivo infection modeling. In this study, an A. baumannii infection was successfully established, through the bath immersion of tail-injured zebrafish embryos, to study the virulence of eight capsule types (K1, K2, K9, K32, K38, K44, K45, and K67). The model revealed itself as capable of discerning the most virulent (K2, K9, K32, and K45), middle (K1, K38, and K67), and the less virulent (K44) strains. Additionally, the infection of the most virulent strains was controlled in vivo resorting to the same technique, with previously identified phages (K2, K9, K32, and K45 phages). Phage treatments were able to increase the average survival from 35.2% to up to 74.1% (K32 strain). All the phages performed equally well. Collectively, the results show the potential of the model to not only evaluate virulence of bacteria such as A. baumannii but also assess novel treatments' effectiveness.

摘要

鲍曼不动杆菌是导致医院感染的主要细菌病原体,其死亡率很高,主要是由于其对抗生素的多重耐药性。荚膜多糖(K 型)是主要的毒力因子。噬菌体是专门感染细菌的病毒,已被用于控制耐药性细菌病原体。特别是,鲍曼不动杆菌噬菌体可以识别存在的 >125 种多样性中的特定荚膜。这种高特异性要求体内鉴定需要噬菌体治疗靶向的最毒力的鲍曼不动杆菌 K 型。目前,斑马鱼胚胎特别受到体内感染建模的关注。在这项研究中,通过尾伤斑马鱼胚胎的浸泡浴成功建立了鲍曼不动杆菌感染,以研究八种荚膜类型(K1、K2、K9、K32、K38、K44、K45 和 K67)的毒力。该模型证明自己能够区分最毒力(K2、K9、K32 和 K45)、中等毒力(K1、K38 和 K67)和低毒力(K44)菌株。此外,通过相同的技术(使用先前鉴定的噬菌体(K2、K9、K32 和 K45 噬菌体)),感染最毒力的菌株的情况也得到了控制。噬菌体处理能够将平均存活率从 35.2%提高到 74.1%(K32 株)。所有的噬菌体都表现得同样好。总的来说,这些结果表明该模型不仅有潜力评估鲍曼不动杆菌等细菌的毒力,还有潜力评估新治疗方法的有效性。

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