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© Research
Scientific Fields
Diseases
Organisms
Applications
Technique

Published in The Cell Surface - 06 Mar 2019

Valsecchi I, Lai J, Stephen-Victor E, Pillé A, Beaussart A, Lo V, Pham C, Aimanianda V, Kwan A, Duchateau M, Giai Gianetto Q, Matondo M, Lehoux M, Sheppard D, Dufrene Y, Bayry J, Iñaki Guijarro J, Sunde M, Latgé J-P

The Cell Surface (2019)

Abstract

The rodlet structure present on the Aspergillus fumigatus conidial surface hides conidia from immune recognition. In spite of the essential biological role of the rodlets, the molecular basis for their self-assembly and disaggregation is not known. Analysis of the soluble forms of conidia-extracted and recombinant RodA by NMR spectroscopy has indicated the importance of disulfide bonds and identified two dynamic regions as likely candidates for conformational change and intermolecular interactions during conversion of RodA into the amyloid rodlet structure. Point mutations introduced into the RODA sequence confirmed that (1) mutation of a single cysteine was sufficient to block rodlet formation on the conidial surface and (2) both presumed amyloidogenic regions were needed for proper rodlet assembly. Mutations in the two putative amyloidogenic regions retarded and disturbed, but did not completely inhibit, the formation of the rodlets in vitro and on the conidial surface. In contrast to the parental conidia, mutant conidia lacking disulfide bridges within RodA or expressing RodA carrying the double (I115S/I146G) mutation activated dendritic cells with the subsequent secretion of proinflammatory cytokines. The immune reactivity of the RodA mutant conidia was not due to a modification in the RodA structure, but to the exposure of different pathogen-associated molecular patterns on the surface as a result of the modification of the rodlet surface layer. The disorganization and loss of the rodlet layer which occur during the early stages of germination, and lead to an anti-fumigatus host immune response, is initiated by the cell wall bound aspartic proteases.

Keywords

Aspergillus fumigatus
hydrophobins
rodlets
RodA
amyloids
https://doi.org/10.1016/j.tcsw.2019.100023