Villoria Recio Miguel, Lee Bo-Hyung, Lillebæk Eva Maria Sternkopf, Kallipolitis Birgitte H, Gahan Cormac G M, Ingmer Hanne, Larsen Marianne Halberg
Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, Food Safety and Zoonoses-University of Copenhagen, Frederiksberg, Denmark.
Alimentary Pharmabotic Centre Microbiome Ireland, University College Cork, Cork, Ireland.
Front Microbiol. 2020 Dec 3;11:588906. doi: 10.3389/fmicb.2020.588906. eCollection 2020.
External signals are crucial for bacteria to sense their immediate environment and fine-tune gene expression accordingly. The foodborne pathogen senses a range of environmental cues in order to activate or deactivate the virulence-inducing transcriptional factor PrfA during transition between infectious and saprophytic lifecycles. Chitin is an abundant biopolymer formed from linked β-(1-4)-N-acetyl-D-glucosamine residues associated with fungi, the exoskeleton of insects and often incorporated into foods as a thickener or stabilizer. evolved to hydrolyse chitin, presumably, to facilitate nutrient acquisition from competitive environments such as soil where the polymer is abundant. Since mammals do not produce chitin, we reasoned that the polymer could serve as an environmental signal contributing to repression of PrfA-dependent expression. This study shows a significant downregulation of the core PrfA-regulon during virulence-inducing conditions in the presence of chitin. Our data suggest this phenomenon occurs through a mechanism that differs from PTS-transport of oligosaccharides generated from either degradation or chitinase-mediated hydrolysis of the polymer. Importantly, an indication that chitin can repress virulence expression of a constitutively active PrfA mutant is shown, possibly mediated via a post-translational modification inhibiting PrfA activity. To our knowledge, this is the first time that chitin is reported as a molecule with anti-virulence properties against a pathogenic bacterium. Thus, our findings identify chitin as a signal which may downregulate the virulence potential of the pathogen and may provide an alternative approach toward reducing disease risk.
外部信号对于细菌感知其周围环境并相应地微调基因表达至关重要。食源性病原体在传染性生命周期和腐生生命周期之间转换时,会感知一系列环境线索,以激活或失活诱导毒力的转录因子PrfA。几丁质是一种丰富的生物聚合物,由与真菌、昆虫外骨骼相关的连接的β-(1-4)-N-乙酰-D-葡萄糖胺残基形成,并且常作为增稠剂或稳定剂添加到食品中。细菌进化出水解几丁质的能力,大概是为了便于从聚合物丰富的竞争环境(如土壤)中获取营养。由于哺乳动物不产生几丁质,我们推测这种聚合物可以作为一种环境信号,有助于抑制PrfA依赖性表达。本研究表明,在存在几丁质的情况下,在诱导毒力的条件下,核心PrfA调控子会显著下调。我们的数据表明,这种现象是通过一种不同于对由聚合物降解或几丁质酶介导的水解产生的寡糖进行磷酸转移酶系统(PTS)转运的机制发生的。重要的是,研究表明几丁质可以抑制组成型活性PrfA突变体的毒力表达,这可能是通过一种抑制PrfA活性的翻译后修饰介导的。据我们所知,这是首次报道几丁质是一种对病原菌具有抗毒力特性的分子。因此,我们的研究结果确定几丁质是一种可能下调病原体毒力潜能的信号,并且可能为降低疾病风险提供一种替代方法。