Antifungal activity of biosynthesized silver nanoparticles from Candida albicans on the strain lacking the CNP41 gene

The upsurge of immunocompromised patients has led to extensive study of fungal infections with Candida albicans being the frontline model of pathogenic yeast in humans. In the quest to find novel antifungal agents, this study reports the potential usage of wild-type C. albicans strain C86 to biosynthesise silver nanoparticles by microwave assisted technique. Visual colour change and UV-spectrophotometer were used for primary detection of silver nanoparticles. Additionally, the FTIR peaks confirm the particles' formation and surface characterisation techniques such as FESEM and EDX suggests that the silver nanoparticles were sized in the range of 30-70 nm. Furthermore, pioneering work of homologous recombination technique was systematically employed to delete uncharacterized gene orf19.3120 (CNP41) in the C86 strain creating the deletion strain C403 of C. albicans. To amalgamate the two significant findings, biosynthesized silver nanoparticles were subjected to antifungal studies by disk diffusion assay on the strain C403 that lacks the gene orf19.3120 (CNP41) of C. albicans. As a synergetic approach, combinational effect was studied by incorporating antifungal drug fluconazole. Both individual and enhanced combinational antifungal effects of silver nanoparticles and fluconazole were observed on genetically modified C403 strain with 40% increase in fold area compared to wild-type C86 strain. This can be attributed to the synergetic effect of the bonding reaction between fluconazole and AgNPs. Taken together, this first-ever interdisciplinary study strongly suggests that the CNP41 gene could play a vital role in drug resistance in this fungal pathogen.publishersversionpublishe

Functional Subunits of Eukaryotic Chaperonin CCT/TRiC in Protein Folding

Molecular chaperones are a class of proteins responsible for proper folding of a large number of polypeptides in both prokaryotic and eukaryotic cells. Newly synthesized polypeptides are prone to nonspecific interactions, and many of them make toxic aggregates in absence of chaperones. The eukaryotic chaperonin CCT is a large, multisubunit, cylindrical structure having two identical rings stacked back to back. Each ring is composed of eight different but similar subunits and each subunit has three distinct domains. CCT assists folding of actin, tubulin, and numerous other cellular proteins in an ATP-dependent manner. The catalytic cooperativity of ATP binding/hydrolysis in CCT occurs in a sequential manner different from concerted cooperativity as shown for GroEL. Unlike GroEL, CCT does not have GroES-like cofactor, rather it has a built-in lid structure responsible for closing the central cavity. The CCT complex recognizes its substrates through diverse mechanisms involving hydrophobic or electrostatic interactions. Upstream factors like Hsp70 and Hsp90 also work in a concerted manner to transfer the substrate to CCT. Moreover, prefoldin, phosducin-like proteins, and Bag3 protein interact with CCT and modulate its function for the fine-tuning of protein folding process. Any misregulation of protein folding process leads to the formation of misfolded proteins or toxic aggregates which are linked to multiple pathological disorders