Paper of the month in March: DGHM has chosen recent publication written by Rita and Annika

| by Steffi Feller

We are honoured that the German Society for Hygiene and Microbiology (DGHM) has chosen the recently published paper, written by our scientists Rita and Annika, for the "Paper of the month" in March 2024:

Secretion of the fungal toxin candidalysin is dependent on conserved precursor peptide sequences

Müller R, König A, Groth S, Zarnowski R, Visser C, Handrianz T, Maufrais C, Krüger T, Himmel M, Lee S, Priest EL, Yildirim D, Richardson JP, Blango MG, Bougnoux ME, Kniemeyer O, d'Enfert C, Brakhage AA, Andes DR, Trümper V, Nehls C, Kasper L, Mogavero S, Gutsmann T, Naglik JR, Allert S, Hube B (2024) Nat Microbiol 9(3), 669-683.

Abstract

The opportunistic fungal pathogen Candida albicans damages host cells via its peptide toxin, candidalysin. Before secretion, candidalysin is embedded in a precursor protein, Ece1, which consists of a signal peptide, the precursor of candidalysin and seven non-candidalysin Ece1 peptides (NCEPs), and is found to be conserved in clinical isolates. Here we show that the Ece1 polyprotein does not resemble the usual precursor structure of peptide toxins. C. albicans cells are not susceptible to their own toxin, and single NCEPs adjacent to candidalysin are sufficient to prevent host cell toxicity. Using a series of Ece1 mutants, mass spectrometry and anti-candidalysin nanobodies, we show that NCEPs play a role in intracellular Ece1 folding and candidalysin secretion. Removal of single NCEPs or modifications of peptide sequences cause an unfolded protein response (UPR), which in turn inhibits hypha formation and pathogenicity in vitro. Our data indicate that the Ece1 precursor is not required to block premature

Congratulations, Rita and Annika!