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

GILMOUR_Q22DTP

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. In this joint studentship between the Gilmour and Hall groups and the Quadram Institute, the student will have broad training opportunities on genome sequencing and the development of molecular biology tools for transposon mutagenesis – all 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.

The student will join a large community of microbiologists based at the Quadram Institute in a brand new, purpose-built building that houses these advanced technologies. The Quadram Institute is part of the Norwich Research Park – and the student will join a large cohort of graduate researchers with exceptional training opportunities.

Informal enquiries: Matthew.Gilmour@quadram.ac.uk or Lindsay.Hall@quadram.ac.uk

References

(those marked with * from supervisory team)

*1. Alcon-Giner C, Dalby MJ, Caim S, Ketskemety J, Shaw A, Sim K, Lawson M, Kiu R, Leclaire C, Chalklen L, Kujawska M, Mitra D, Fardus-Reid F, Belteki, G, McColl K, Swann JR, Kroll JS, Clarke P, Hall LJ. Microbiota supplementation with Bifidobacterium and Lactobacillus modifies the preterm infant gut microbiota and metabolome: an observational study. Cell Reports Medicine (2020). doi: 10.1016/j.xcrm.2020.100077

*2. Lopez-Tello J, Schofield Z, Kiu R, Dalby MJ, van Sinderen D, Le Gall G, Sferruzzi-Perri AN, and Hall LJ. Maternal microbiota Bifidobacterium promotes placental vascularization, nutrient transport and fetal growth in mice. BioRxiv. 2021. doi: https://doi.org/10.1101/2021.07.23.453407

*3. Reimer A, Weedmark K, Petkau A, Peterson CL, Walker M, Knox N, Kent H, Mabon P, Berry C, Tyler S, Tschetter L, Jerome M, Allen V, Hoang L, Bekal S, Clark C, Nadon C, Van Domselaar G, Pagotto F, Graham M, Farber J, and Gilmour M. Shared genome analyses of notable listeriosis outbreaks, highlighting the critical importance of epidemiological evidence, input datasets and interpretation criteria. Microbial Genomics. 2019 Jan;5(1):e000237. https://doi.org/10.1099/mgen.0.000237