Dataset Information

Delineating the Biofilm Inhibition Mechanisms of Phenolic and Aldehydic Terpenes against Cryptococcus neoformans.

ABSTRACT: The recalcitrant biofilm formed by fungus Cryptococcus neoformans is a life-threatening pathogenic condition responsible for further intensifying cryptococcosis. Considering the enhanced biofilm resistance and toxicity of synthetic antifungal drugs, the search for efficient, nontoxic, and cost-effective natural therapeutics has received a major boost. Phenolic (thymol and carvacrol) and aldehydic (citral) terpenes are natural and safe alternatives capable of efficient microbial biofilm inhibition. However, the biofilm inhibition mechanism of these terpenes still remains unclear. In this study, we adopted an integrative biophysical and biochemical approach to elucidate the hierarchy of their action against C. neoformans biofilm cells. The microscopic analysis revealed disruption of the biofilm cell surface with elevation in surface roughness and reduction in cell height. Although all terpenes acted through ergosterol biosynthesis inhibition, the phenolic terpenes also selectively interacted via ergosterol binding. Further, the alterations in the fatty acid profile in response to terpenes attenuated the cell membrane fluidity with enhanced permeability, resulting in pore formation and efflux of the K+/intracellular content. Additionally, mitochondrial depolarization caused higher levels of reactive oxygen species, which led to increased lipid peroxidation and activation of the antioxidant defense system. Indeed, the oxidative stress caused a significant decline in the amount of extracellular polymeric matrix and capsule sugars (mannose, xylose, and glucuronic acid), leading to a reduced capsule size and an overall negative charge on the cell surface. This comprehensive data revealed the mechanistic insights into the mode of action of terpenes on biofilm inhibition, which could be exploited for formulating novel anti-biofilm agents.

SUBMITTER: Kumari P

PROVIDER: S-EPMC6822124 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Delineating the Biofilm Inhibition Mechanisms of Phenolic and Aldehydic Terpenes against <i>Cryptococcus neoformans</i>.

Kumari Poonam P Arora Neha N Chatrath Apurva A Gangwar Rashmi R Pruthi Vikas V Poluri Krishna Mohan KM Prasad Ramasare R

ACS omega 20191015 18

The recalcitrant biofilm formed by fungus <i>Cryptococcus neoformans</i> is a life-threatening pathogenic condition responsible for further intensifying cryptococcosis. Considering the enhanced biofilm resistance and toxicity of synthetic antifungal drugs, the search for efficient, nontoxic, and cost-effective natural therapeutics has received a major boost. Phenolic (thymol and carvacrol) and aldehydic (citral) terpenes are natural and safe alternatives capable of efficient microbial biofilm in ...[more]

PMID: 31681870

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Project description:Cryptococcus neoformans is an opportunistic fungal pathogen that causes meningitis in >152,000 immunocompromised individuals annually, leading to 112,000 yearly deaths. The four classes of existing antifungal agents target plasma membrane sterols (ergosterol), nucleic acid synthesis, and cell wall synthesis. Existing drugs are not highly effective against Cryptococcus, and antifungal drug resistance is an increasing problem. A novel antimicrobial compound, a eumelanin-inspired indoylenepheyleneethynylene, EIPE-1, was synthesized and has antimicrobial activity against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MSRA), but not towards Gram-negative organisms. Based on EIPE-1's antibacterial activity, we hypothesized that EIPE-1 could have antifungal activity. For these studies, we tested EIPE-1 against C. neoformans strain H99 and 6 additional cryptococcal clinical isolates. We examined antifungal activity, cytotoxicity, effects on fungal gene expression, and mechanism of action of EIPE-1. Results showed that EIPE-1 has fungicidal effects on seven cryptococcal strains with MICs ranging from 1.56 to 3.125 μg/mL depending on the strain, and it is non-toxic to mammalian cells. We conducted scanning and transmission electron microscopy on the exposed cells to examine structural changes to the organism following EIPE-1 treatment. Cells exposed displayed structural changes to their cell wall and membranes, with internal contents leaking out of the cells. To understand the effect of EIPE-1 on fungal gene expression, RNA sequencing was conducted. Results showed that EIPE-1 affects several processes involved stress response, ergosterol biosynthesis, capsule biosynthesis, and cell wall attachment and remodeling. Therefore, our studies demonstrate that EIPE-1 has antifungal activity against C. neoformans, which affects both cellular structure and gene expression of multiple fungal pathways involved in cell membrane stability and viability.

Dataset Information

Delineating the Biofilm Inhibition Mechanisms of Phenolic and Aldehydic Terpenes against Cryptococcus neoformans.

Publications

Delineating the Biofilm Inhibition Mechanisms of Phenolic and Aldehydic Terpenes against <i>Cryptococcus neoformans</i>.

Similar Datasets

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