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

Abstract

Paracoccidioides brasiliensis and Paracoccidioides lutzii are dimorphic fungi and are the etiological agents of paracoccidioidomycosis (PCM). Adhesion is one of the most important steps in infections with Paracoccidioides 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 Paracoccidioides, thus inhibiting infection and preventing the disease. We used two phage display libraries to select peptides that strongly bind to the Paracoccidioides 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 Paracoccidioides to pneumocytes in vitro 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 Galleria mellonella from Paracoccidioides infection by treating G. mellonella larvae with the different peptides prior to infection with Paracoccidioides and observing larval survival. The results show that all of the peptides tested increased the survival of the larvae infected with P. brasiliensis by up to 64% and by up to 60% in those infected with P. lutzii. These data may open new horizons for therapeutic strategies to prevent PCM, and anti-adhesion therapy could be an important strategy.

Rearing and Maintenance of Galleria mellonella and Its Application to Study Fungal Virulence

“…Here, the low virulence of the knockout mutant strain Δ coll was probably related to a weak attachment in the larva soft tissues, as collagen is an essential protein widely distributed among living organisms, including G. mellonella . Pre-treatment of G. mellonella with peptides that inhibit the cell wall adhesion of Paracoccidiodes brasiliensis and P. lutzii increased the survival of larvae from 64% and 60% respectively, in addition to the hemocytes count [ 46 ]. The lack of difference in the knockout mutant strain Δ endo could be related with redundancy in the pathways controlled by this large family of proteins.…”

Th17-Inducing Cytokines IL-6 and IL-23 Are Crucial for Granuloma Formation during Experimental Paracoccidioidomycosis

“…Paracoccidioidomycosis (PCM), a systemic mycosis characterized by chronic and granulomatous inflammation, is caused by the thermally dimorphic fungus Paracoccidioides brasiliensis and Paracoccidioides lutzii ( 1 ). PCM has high incidence in several countries of Latin America and represents the eighth cause of death among infectious and parasitic diseases.…”

Micronized curcumin fabricated by supercritical CO 2 to improve antibacterial activity against Pseudomonas aeruginosa

“…The adhesion of microorganisms to host cells is a prerequisite for colonization and infection [37] and biofilm is one of the key factors that is conducive for infection and drug resistance [38]. Herein, original CM and CM NPs were investigated to further explore their ability to prevent the adhesion to mouse pulmonary epithelial cells (PECs), and inhibit the biofilm formation of P. aeruginosa.…”