Peptides Derived from a Phage Display Library Inhibit Adhesion and Protect the Host against Infection by Paracoccidioides brasiliensis and Paracoccidioides lutzii

Abstract

<i>Paracoccidioides brasiliensis</i> and <i>Paracoccidioides lutzii</i> are dimorphic fungi and are the etiological agents of paracoccidioidomycosis (PCM). Adhesion is one of the most important steps in infections with <i>Paracoccidioide</i>s and is responsible for the differences in the virulence of isolates of these fungi. Because of the importance of adhesion to the establishment of an infection, this study focused on the preliminary development of a new therapeutic strategy to inhibit adhesion by <i>Paracoccidioides</i>, thus inhibiting infection and preventing the disease. We used two phage display libraries to select peptides that strongly bind to the <i>Paracoccidioides</i> cell wall to inhibit adhesion to host cells and extracellular matrix (ECM) components (laminin, fibronectin, and type I and type IV collagen). This approach allowed us to identify four peptides that inhibited up to 64% of the adhesion of <i>Paracoccidioides</i> to pneumocytes <i>in vitro</i> and inhibited the adhesion to the ECM components by up to 57%. Encouraged by these results, we evaluated the ability of these peptides to protect <i>Galleria mellonella</i> from <i>Paracoccidioides</i> infection by treating <i>G. mellonella</i> larvae with the different peptides prior to infection with <i>Paracoccidioides</i> and observing larval survival. The results show that all of the peptides tested increased the survival of the larvae infected with <i>P. brasiliensis</i> by up to 64% and by up to 60% in those infected with <i>P. lutzii</i>. These data may open new horizons for therapeutic strategies to prevent PCM, and anti-adhesion therapy could be an important strategy.