Probiotics and Pathogens - A Microbial Tug of War for the Host

在对抗感染方面，我们并不孤单-我们的肠道微生物群很可能对入侵的细菌病原体提供保护作用。双歧杆菌是影响微生物群落动态和宿主免疫发育的基础微生物群属。我们的团队一直在利用这些特性来研究双歧杆菌作为促进健康的益生菌（1），同时也研究这种益生菌在生命早期阶段的生理益处，包括在怀孕期间（2）.与肠道微生物群的支持作用相反，入侵病原体有许多策略来逃避宿主的保护性免疫反应。单核细胞增生李斯特菌是“专业的细胞内病原体”，与重大食源性爆发（3）和严重疾病或死亡有关，因为它非常有能力引起从肠道传播到血液，大脑甚至胎儿的全身性感染。本项目旨在研究宿主细胞与双歧杆菌之间的潜在动态关系，并利用基因组测序和转座子诱变分子生物学工具的开发来探索这些微生物-宿主反应的机制。在此之后，将使用组织培养模型来研究双歧杆菌如何与宿主上皮细胞和免疫细胞相互作用，然后在李斯特菌的存在下，双歧杆菌如何调节这种病原体的侵袭力。

We are not alone when it comes to fighting off infections - our commensal gut microbiota very likely provides a protective effect against invading bacterial pathogens. Bifidobacterium are a foundational microbiota genus influencing microbial community dynamics and host immune development. Our group has been exploiting these properties to study Bifidobacterium as a health-promoting probiotic (1), while also investigating the physiological benefits of this commensal at early life stages, including during pregnancy (2).Contrary to the support role of commensal microbiota, invasive pathogens have numerous strategies to evade the protective immune response of the host. Listeria monocytogenes is 'professional intracellular pathogen' and associated with significant foodborne outbreaks (3) and severe illness or death, as it is highly capable of causing systemic infections that spread from the gut to the blood, brain, or even foetus. This project seeks to investigate the potentially dynamic relationship that occurs at host cells when presented with Bifidobacterium that are tuned to promote health, while also facing highly invasive Listeria that seek to counteract these defences.Genome sequencing and the development of molecular biology tools for transposon mutagenesis will be used to explore mechanisms underpinning these microbe-host responses. Following this, a tissue culture model will be used to study how Bifidobacteirum interacts with host epithelial and immune cells, and then in the presence of Listeria, how Bifidobacteirum may modulate the invasiveness of this pathogen.