Exploration of Mycelial Proteins and Shikonin Mediated Growth Inhibition of Aspergillus Terreus using Proteomics Approach

Abstract

Aspergillus terreus has emerged as an important opportunistic fungal pathogen. There has been a significant increase in cancer incidences, viral infections, and organ transplantation that lead to secondary fungal diseases. A. terreus causes mortality, high persistence, lack of early diagnosis, and inherent Amphotericin B (AmB) resistance. Morphological changes to the inhaled conidia are very crucial during invasive infections. Molecular methods help to explain active genes and their products at the various stages of development. Despite this very little has been studied regarding the determinants contributing to the pathogenesis, including AmB intrinsic resistance, and biomolecules associated with mycelia and biofilm formation. In documented work, we observed that the mycelia of A. terreus (NCCPF-860035) a clinical isolates rich in proteins from energy metabolism, ribosome biogenesis, oxidative homeostasis, cell wall, and structural components were revealed using nLC-ESI-MS/MS method. Majorly, important proteins (Catalase, superoxide dismutase, Hsp90, and Hsp70) may augment resistance against AmB in A. terreus. Additionally, SEM images and predicted biofilm-related secretory and adhesin proteins evident extracellular matrix (ECM) formation in A. terreus. Besides this being intrinsically resistant to the gold standard AmB therapy, the cure of these infections is a clinical threat now. Thus, improved therapeutics or new effective lead molecules are thus obviously the call of clinical professionals. Hence, in the present study, we have evaluated the phytochemicals (SHK, GA, CA, and QRT) against A. terreus. SHK showed higher efficacy (MIC50;2 µg/ml) among all the tested phytochemicals against planktonic as well as biofilm of A. terreus. The tested standard drugs (AmB, FLC, and ITC) were found less susceptible as showed higher MIC50values for both planktonic and biofilm cultures of A. terreus. Differential proteome analysis was conducted to understand the inhibitory effect of SHK. The proteins/ enzymes from signaling