ABSTRACT
Cryptococcus neoformans is a multidrug-resistant pathogen responsible for infections in immunocompromised patients. Here, itraconazole (ITR), a commercial antifungal drug with low effectiveness against C. neoformans, was combined with different synthetic antimicrobial peptides (SAMPs), Mo-CBP3-PepII, RcAlb-PepII, RcAlb-PepIII, PepGAT, and PepKAA. The Mo-CBP3-PepII was designed based on the sequence of MoCBP3, purified from Moringa oleifera seeds. RcAlb-PepII and RcAlb-PepIII were designed using Rc-2S-Alb, purified from Ricinus communis seed cakes. The putative sequence of a chitinase from Arabidopsis thaliana was used to design PepGAT and PepKAA. All SAMPs have a positive liquid charge and a hydrophobic potential ranging from 41-65%. The mechanisms of action responsible for the combined effect were evaluated for the best combinations using fluorescence microscopy (FM). The synthetic peptides enhanced the activity of ITR by 10-fold against C. neoformans. Our results demonstrated that the combinations could induce pore formation in the membrane and the overaccumulation of ROS on C. neoformans cells. Our findings indicate that our peptides successfully potentialize the activity of ITR against C. neoformans. Therefore, synthetic peptides are potential molecules to assist antifungal agents in treating Cryptococcal infections.
ABSTRACT
The indiscriminate use of antibiotics is associated with the appearance of bacterial resistance. In light of this, plant-based products treating infections are considered potential alternatives. Lectins are a group of proteins widely distributed in nature, capable of reversibly binding carbohydrates. Lectins can bind to the surface of pathogens and cause damage to their structure, thus preventing host infection. The antimicrobial activity of plant lectins results from their interaction with carbohydrates present in the bacterial cell wall and fungal membrane. The data about lectins as modulating agents of antibiotic activity, potentiates the effect of antibiotics without triggering microbial resistance. In addition, lectins play an essential role in the defense against fungi, reducing their infectivity and pathogenicity. Little is known about the antiviral activity of plant lectins. However, their effectiveness against retroviruses and parainfluenza is reported in the literature. Some authors still consider mannose/ glucose/N-Acetylglucosamine binding lectins as potent antiviral agents against coronavirus, suggesting that these lectins may have inhibitory activity against SARS-CoV-2. Thus, it was found that plant lectins are an alternative for producing new antimicrobial drugs, but further studies still need to decipher some mechanisms of action.
