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巴氏犬菌的 shotgun 蛋白质组学分析为研究其对缺铁的生理反应提供了新视角,并揭示了一些在百日咳鲍特菌中缺失的潜在新毒力决定因子。

Shotgun proteomic analysis of Bordetella parapertussis provides insights into the physiological response to iron starvation and potential new virulence determinants absent in Bordetella pertussis.

机构信息

CINDEFI (UNLP CONICET La Plata), Facultad de Ciencias Exactas, Universidad Nacional de La Plata, La Plata, Argentina.

Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.

出版信息

J Proteomics. 2019 Aug 30;206:103448. doi: 10.1016/j.jprot.2019.103448. Epub 2019 Jul 17.

Abstract

Bordetella parapertussis is one of the pathogens that cause whooping cough. Even though its incidence has been rising in the last decades, this species remained poorly investigated. This study reports the first extensive proteome analysis of this bacterium. In an attempt to gain some insight into the infective phenotype, we evaluated the response of B. parapertussis to iron starvation, a critical stress the bacteria face during infection. Among other relevant findings, we observed that the adaptation to this condition involves significant changes in the abundance of two important virulence factors of this pathogen, namely, adenylate cyclase and the O-antigen. We further used the proteomic data to search for B. parapertussis proteins that are absent or classified as pseudogenes in the genome of Bordetella pertussis to unravel differences between both whooping cough causative agents. Among them, we identified proteins involved in stress resistance and virulence determinants that might help to explain the differences in the pathogenesis of these species and the lack of cross-protection of current acellular vaccines. Altogether, these results contribute to a better understanding of B. parapertussis biology and pathogenesis. SIGNIFICANCE: Whooping cough is a reemerging disease caused by both Bordetella pertussis and Bordetella parapertussis. Current vaccines fail to induce protection against B parapertussis and the incidence of this species has been rising over the years. The proteomic analysis of this study provided relevant insights into potential virulence determinants of this poorly-studied pathogen. It further identified proteins produced by B. parapertussis not present in B. pertussis, which might help to explain both the differences on their respective infectious process and the current vaccine failure. Altogether, the results of this study contribute to the better understanding of B. parapertussis pathogenesis and the eventual design of improved preventive strategies against whooping cough.

摘要

百日咳博德特氏菌是引起百日咳的病原体之一。尽管在过去几十年中,其发病率一直在上升,但该物种的研究仍很不充分。本研究报告了对该细菌进行的首次广泛的蛋白质组分析。为了深入了解感染表型,我们评估了百日咳博德特氏菌对缺铁的反应,这是细菌在感染过程中面临的关键应激。在其他相关发现中,我们观察到,适应这种情况涉及到该病原体两种重要毒力因子的丰度的显著变化,即腺苷酸环化酶和 O-抗原。我们进一步利用蛋白质组数据搜索百日咳博德特氏菌的蛋白质,这些蛋白质在百日咳博德特氏菌的基因组中不存在或被归类为假基因,以揭示这两种引起百日咳的病原体之间的差异。其中,我们鉴定出了与应激抗性和毒力决定因素相关的蛋白质,这可能有助于解释这些物种在发病机制上的差异以及当前无细胞疫苗缺乏交叉保护作用的原因。总之,这些结果有助于更好地了解百日咳博德特氏菌的生物学和发病机制。

意义

百日咳是由百日咳博德特氏菌和百日咳博德特氏菌引起的一种重新出现的疾病。当前的疫苗未能诱导对百日咳博德特氏菌的保护作用,并且该物种的发病率近年来一直在上升。本研究的蛋白质组分析为该研究较少的病原体的潜在毒力决定因素提供了重要的见解。它进一步鉴定出了百日咳博德特氏菌产生的而在百日咳博德特氏菌中不存在的蛋白质,这可能有助于解释它们各自感染过程中的差异以及当前疫苗失败的原因。总之,本研究的结果有助于更好地了解百日咳博德特氏菌的发病机制,并最终设计出针对百日咳的改进预防策略。

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