Molecular characterisation of Candidalysin-epithelial membrane interactions

Abstract

Candidalysin is a newly-discovered cytolytic peptide toxin that is secreted by the fungal pathogen Candida albicans [1], the causative agent of thrush which causes millions of mucosal infections annually [2]. Candidalysin is essential for the ability of C. albicans to activate epithelial cells and induce cell damage, and is critical for mucosal pathogenicity in vivo [1, 3, 4]. This landmark discovery represents a seminal advance in our understanding of fungal pathogenesis. This project aims to build on these discoveries to identify the key membrane components that Candidalysin interacts with in order to damage and activate epithelial cells.




References:
[1]

Moyes DL, Wilson D, Richardson JP, Tang SX, Wernecke J, Höfs S, Gratacap RL, Mogavero S, Robbins J, Runglall M, Murciano C, Blagojevic M, Thavaraj S, Förster TM, Hebecker B, Kasper L, Vizcay G, Iancu SI, Kichik N, Häder A, Kurzai O, Cota E, Bader O, Wheeler RT, Gutsmann T, Hube B and Naglik JR (2016). Candidalysin: A fungal peptide toxin critical for mucosal infection. Nature 532, 64-68

[2]

Brown GD, Denning DW, Gow NA, Levitz SM, Netea MG and White TC. Hidden killers: human fungal infections. Sci Transl Med. 2012 Dec 19;4(165):165rv13

[3]

Moyes DL Runglall M, Murciano C, Shen C, Nayar D, Thavaraj S, Kohli A, Islam A, Mora-Montes M, Challacombe SJ, and Naglik JR (2010). A biphasic innate immune MAPK response discriminates between the yeast and hyphal forms of Candida albicans in Epithelial Cells. Cell Host and Microbe 8 (3), 225-35

[4]

Moyes DL, Shen C, Murciano C, Runglall M, Richardson JP, Arno M, Aldecoa-Otalora E, Islam A and Naglik JR (2014). Protection against epithelial damage during Candida albicans infection is mediated by PI3K/AKT signaling. Journal of Infectious Diseases 209 (11), 1816-1826

[5]

Howorka S. (2016) Changing of the guard: DNA nanostructures mimic membrane proteins. Science. 352 (6288), 890-891


Biological Areas:

Chemical Biology
Microbiology

BBSRC Area:

Plants, microbes, food and sustainability