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Advisor(s)
Abstract(s)
Blad polypeptide comprises residues 109–281 of Lupinus albus b-conglutin precursor. It
occurs naturally as a major subunit of an edible, 210 kDa oligomer which accumulates to
high levels, exclusively in the cotyledons of Lupinus seedlings between the 4th and 14th
day after the onset of germination. Blad-containing oligomer (BCO) exhibits a potent
and broad spectrum fungicide activity toward plant pathogens and is now on sale in
the US under the tradename FractureTM. In this work we demonstrate its antifungal
activity toward human pathogens and provide some insights on its mode of action. BCO
bioactivity was evaluated in eight yeast species and compared to that of amphotericin
B (AMB). BCO behaved similarly to AMB in what concerns both cellular inhibition and
cellular death. As a lectin, BCO binds strongly to chitin. In addition, BCO is known to
possess ‘exochitinase’ and ‘endochitosanase’ activities. However, no clear disruption
was visualized at the cell wall after exposure to a lethal BCO concentration, except
in cell buds. Immunofluorescent and immunogold labeling clearly indicate that BCO
enters the cell, and membrane destabilization was also demonstrated. The absence
of haemolytic activity, its biological origin, and its extraordinary antifungal activity are the
major outcomes of this work, and provide a solid background for a future application as
a new antifungal therapeutic drug. Furthermore, its predictable multisite mode of action
suggests a low risk of inducing resistance mechanisms, which are now a major problem
with other currently available antifungal drugs.
Description
Keywords
Candida albicans antifungal natural product pathogenic yeast protein-based
Pedagogical Context
Citation
Pinheiro AM, Carreira A, Rollo F, Fernandes R, Ferreira RB and Monteiro SA (2016) Blad-Containing Oligomer Fungicidal Activity on Human Pathogenic Yeasts. From the Outside to the Inside of the Target Cell. Front. Microbiol. 7:1803.
Publisher
Maria Tereza dos Santos Correia (ed.)