Many bacterial pathogens use the Type VI secretion system (T6SS) to deliver varied toxic ‘effector’ proteins directly into target cells. The T6SS plays a key role in the virulence and competitiveness of diverse Gram-negative bacteria, including important human pathogens. Whilst in some cases the T6SS can be used to directly attack host cells, as a classical virulence factor, the primary role of the T6SS is believed to be during inter-bacterial competition, when bacteria use the T6SS to deliver anti-bacterial effectors into other bacterial cells, killing or inhibiting their rivals. There is now increasing evidence that anti-bacterial T6SSs play a key role in shaping diverse polymicrobial communities. Importantly, we have recently discovered that bacteria can also use T6SS-delivered effectors specifically to target microbial fungi, including important fungal pathogens. Bacteria and fungi frequently co-exist in polymicrobial communities, including the human microbiota and disease-causing infections, and we believe that anti-fungal T6SS activity is likely to represent a widespread determinant of microbial community composition and dynamics, something critical to many aspects of human health and disease. Indeed, diseases caused by fungal pathogens represent a significant and often therapeutically-challenging healthcare problem.
We study the roles of the T6SS, its regulation, the mechanisms of effector delivery, and the mode-of-action of T6SS-dependent effector proteins. We utilise a wide range of molecular, cellular and genetic approaches, and focus on representative examples of Gram-negative bacterial pathogens and fungal pathogens. In this project, we will study regulation of T6SS-mediated anti-fungal activity in an opportunistic bacterial pathogen. We aim to determine the response of the bacteria to the presence of fungal cells and how detection of fungal cells may feed into the regulation of anti-fungal T6SS activity, including expression of anti-fungal effectors. We will also examine how this regulation varies between clinical and environmental bacteria. The student undertaking this project will gain experience in a number of state-of-the-art molecular, cell biology and ‘omics’ techniques; a strong grounding in microbiology and molecular biology; and opportunities to engage with the international research community, including our world-leading collaborators, and the general public.
- Trunk, K., Peltier, J., Liu, Y., Dill, B.D., Walker, L., Gow, N.A.R., Stark, M.J.R., Quinn, J., Strahl, H., Trost, M. & Coulthurst, S.J. (2018) The Type VI secretion system deploys anti-fungal effectors against microbial competitors. Nature Microbiology, 3, 920–931.
- Coulthurst, S.J. (2019) The Type VI secretion system: a versatile bacterial weapon. Microbiology, 165, 503–515.