Luu Laurence Don Wai, Zhong Ling, Kaur Sandeep, Raftery Mark J, Lan Ruiting
School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia.
Bioanalytical Mass Spectrometry Facility, University of New South Wales, Sydney, NSW, Australia.
Front Cell Infect Microbiol. 2021 Apr 13;11:660280. doi: 10.3389/fcimb.2021.660280. eCollection 2021.
The genus is divided into two groups: classical and non-classical. , and are known as classical bordetellae, a group of important human pathogens causing whooping cough or whooping cough-like disease and hypothesized to have evolved from environmental non-classical bordetellae. infections have increased globally driving the need to better understand these pathogens for the development of new treatments and vaccines. One unexplored component in is the role of serine, threonine and tyrosine phosphorylation. Therefore, this study characterized the phosphoproteome of classical bordetellae and examined its potential role in biology and virulence. Applying strict identification of localization criteria, this study identified 70 unique phosphorylated proteins in the classical group with a high degree of conservation. Phosphorylation was a key regulator of metabolism with proteins involved in gluconeogenesis, TCA cycle, amino acid and nucleotide synthesis significantly enriched. Three key virulence pathways were also phosphorylated including type III secretion system, alcaligin synthesis and the BvgAS master transcriptional regulatory system for virulence genes in . Seven new phosphosites were identified in BvgA with 6 located in the DNA binding domain. Of the 7, 4 were not present in non-classical bordetellae. This suggests that serine/threonine phosphorylation may play an important role in stabilizing/destabilizing BvgA binding to DNA for fine-tuning of virulence gene expression and that BvgA phosphorylation may be an important factor separating classical from non-classical bordetellae. This study provides the first insight into the phosphoproteome of classical species and the role that Ser/Thr/Tyr phosphorylation may play in biology and virulence.
经典型和非经典型。百日咳博德特氏菌、副百日咳博德特氏菌和支气管败血博德特氏菌被称为经典博德特氏菌，是一组引起百日咳或百日咳样疾病的重要人类病原体，据推测是从环境中的非经典博德特氏菌进化而来。全球范围内百日咳博德特氏菌感染有所增加，这推动了为开发新的治疗方法和疫苗而更好地了解这些病原体的需求。百日咳博德特氏菌中一个未被探索的成分是丝氨酸、苏氨酸和酪氨酸磷酸化的作用。因此，本研究对经典博德特氏菌的磷酸化蛋白质组进行了表征，并研究了其在百日咳博德特氏菌生物学和毒力中的潜在作用。应用严格的定位标准鉴定，本研究在经典百日咳博德特氏菌群中鉴定出70种独特的磷酸化蛋白质，具有高度的保守性。磷酸化是百日咳博德特氏菌代谢的关键调节因子，参与糖异生、三羧酸循环、氨基酸和核苷酸合成的蛋白质显著富集。三个关键的毒力途径也发生了磷酸化，包括III型分泌系统、产碱素合成以及百日咳博德特氏菌中毒力基因的BvgAS主转录调节系统。在BvgA中鉴定出七个新的磷酸化位点，其中六个位于DNA结合结构域。在这七个位点中，有四个在非经典博德特氏菌中不存在。这表明丝氨酸/苏氨酸磷酸化可能在稳定/破坏BvgA与DNA的结合以微调毒力基因表达方面发挥重要作用，并且BvgA磷酸化可能是区分经典博德特氏菌和非经典博德特氏菌的重要因素。本研究首次深入了解了经典百日咳博德特氏菌物种的磷酸化蛋白质组以及丝氨酸/苏氨酸/酪氨酸磷酸化在百日咳博德特氏菌生物学和毒力中可能发挥的作用。
