Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia.
Microbiome and Cancer Division, German Cancer Research Center (DKFZ), Heidelberg, Germany.
PLoS Genet. 2023 Apr 26;19(4):e1010737. doi: 10.1371/journal.pgen.1010737. eCollection 2023 Apr.
Diphtheria is a respiratory disease caused by Corynebacterium diphtheriae. While the toxin-based vaccine has helped control outbreaks of the disease since the mid-20th century there has been an increase in cases in recent years, including systemic infections caused by non-toxigenic C. diphtheriae strains. Here we describe the first study of gene essentiality in C. diphtheriae, providing the most-dense Transposon Directed Insertion Sequencing (TraDIS) library in the phylum Actinobacteriota. This high-density library has allowed the identification of conserved genes across the genus and phylum with essential function and enabled the elucidation of essential domains within the resulting proteins including those involved in cell envelope biogenesis. Validation of these data through protein mass spectrometry identified hypothetical and uncharacterized proteins in the proteome which are also represented in the vaccine. These data are an important benchmark and useful resource for the Corynebacterium, Mycobacterium, Nocardia and Rhodococcus research community. It enables the identification of novel antimicrobial and vaccine targets and provides a basis for future studies of Actinobacterial biology.
白喉是一种由白喉棒状杆菌引起的呼吸道疾病。自 20 世纪中叶以来，基于毒素的疫苗帮助控制了该病的爆发，但近年来病例有所增加，包括由非产毒白喉棒状杆菌菌株引起的全身感染。在这里，我们描述了对白喉棒状杆菌基因必需性的首次研究，提供了放线菌门中最密集的转座子定向插入序列（TraDIS）文库。该高密度文库允许在属和门水平上鉴定具有必需功能的保守基因，并阐明了由此产生的蛋白质中的必需结构域，包括参与细胞包膜生物发生的那些结构域。通过蛋白质质谱法对这些数据进行验证，鉴定了蛋白质组中假定的和未表征的蛋白，这些蛋白也存在于疫苗中。这些数据是对棒状杆菌、分枝杆菌、诺卡氏菌和红球菌研究界的重要基准和有用资源。它能够识别新型抗菌和疫苗靶标，并为未来的放线菌生物学研究提供基础。
