Friday, 18 August 2017 10:09

Eucalyptus compound inhibits Candida biofilms

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Published in mBiosphere

Fungal infections are a serious problem in the clinic and in agriculture—a problem that some scientists argue doesn’t receive enough research attention. This blog has recently highlighted the emerging infectious fungus Candida auris, which has only recently been recognized to cause disease in people, but it’s another Candida species, Candida albicans, that is the most common cause of invasive candidemia.

C. albicans can grow as yeast, pseudohyphal and hyphal morphologies, and these different cell shapes play different roles in immune evasion, tissue invasion and drug resistance. All of these morphologies are also required for the fungus to form biofilms, which it does very well on both tissue and plastic. New research from Antimicrobial Agents and Chemotherapy reports on the antibiofilm activity of eucarobustol E, a bioactive compound derived from eucalyptus.

AACJournal: In vitro antibiofilm activity of eucarobustol E against Candida albicans

In their study, first author Rui-Huan Liu and senior scientist Ling-Yi Kong led a scientific team investigating eucarobustol E (EE), which they showed has broad-spectrum antifungal activity. The team then tested the ability of EE to inhibit biofilm formation and to disrupt mature biofilms, since Candida biofilms on plastic indwelling devices (like catheters or IV lines) are thought to seed systemic infections. Treatment with EE both eliminated mature biofilms and inhibited new biofilm formation on plastic, suggesting potential clinical applications for the compound.

EE and C albicansScanning electron micrograph of C. albicans biofilm inhibition with different EE concentrations. Source.

How does EE inhibit biofilms? The team determined that EE treatment prevents a change in cell surface hydrophobicity (required for cells to stick to surfaces and to other cells) and also blocks a change from yeast to hyphal cell morphology (required for biofilm maturation) (see image, right). Using RNA-seq technologies, the researchers discovered that EE alters C. albicans gene expression, including a large number of genes involved in biofilm formation. In the presence of EE, 4 genes that are required for hyphal cell formation and maintenance (EED1, UME6, HGC1 and ECE1) were downregulated, while a negative regulator of hyphal growth (NRG1) was upregulated. This genetic reprogramming inhibits the fungal cells’ ability to form biofilms.

Another mechanism may contribute to biofilm inhibition: a difference in sterol metabolism. EE treatment decreased ergosterol production, and increased farnesol secretion. Farnesol is a sterol precursor that also acts as a quorum-sensing molecule: when cells detect it at sufficient concentrations, it promotes growth in the yeast cell form. Farnesol biosynthesis gene (DPP3) was upregulated in EE-treated cells. The inability to achieve the proper mix of yeast and hyphal cell forms from both genetic reprograming and increased farnesol production contributed to the anti-biofilm properties of EE.

Like antibacterial resistance, antifungal-resistant infections are increasing in patients. Because eukaryotic fungi have cellular structures and processes similar to human cells, drugs that target fungal cells but not human cells (and thus avoid toxic side-effects) are harder to identify. The scientists here demonstrate that EE is nontoxic in cell culture, but the next step is to show that the compound remains active (and nontoxic) when treating in vivo infections.

Last modified on Monday, 21 August 2017 13:12
Julie Wolf

Julie Wolf is the ASM Science Communications Specialist. She contributes to the ASM social media and blog network and hosts the Meet the Microbiologist podcast. She also runs workshops at ASM conferences to help scientists improve their own communication skills. Follow Julie on Twitter for more ASM and microbiology highlights at @JulieMarieWolf.

Julie earned her Ph.D. from the University of Minnesota, focusing on medical mycology and infectious disease. Outside of her work at ASM, she maintains a strong commitment to scientific education and teaches molecular biology at the community biolab, Genspace. She lives in beautiful New York City.