Identification of virulence factors in Candida Auris and antifungal activity of monoterpene phenols against this pathogen
Date
2020
Authors
Shaban, Siham
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
Emergence of Candida auris has been described as a global health threat due to its ability to
cause invasive infections with high mortality rate and its multidrug resistance propensity.
Alternative antifungal strategy along with novel antifungal drugs are required to target this
newly emerged fungal organism and its pathogenicity. Anti-virulence approach and
combination therapy have been proposed in recent years. Essential oils rich in phenolic
monoterpenes are well known for their significant in vitro and in vivo anti C. albicans activity.
They have also been reported to synergize with the conventional antifungal drugs and have
shown anti-virulence effect against Candida species other than C. auris. This study
investigated the virulence factors in C. auris, evaluated the antifungal activity of selected
monoterpene phenols (eugenol, methyl eugenol, carvacrol and thymol) against C. auris,
combination antifungal activity of the most effective phenolic compound with antifungal drugs,
and determined effect of the most active compound on positive pathogenicity markers of C.
auris.
Antifungal susceptibility profile of 25 clinical isolates of C. auris against antifungal agents as
well as against phenolic compounds was obtained using micro broth dilution method following
CLSI guidelines. Combination of the most active phenolic compound with antifungal drugs
was determined by calculating the fractional inhibitory concentration index (FICI) based on
the zero-interaction theory of Loewe additivity. The virulence factors such as (adherence,
morphogenesis, phospholipase and proteinase production) of C. auris isolates were
characterized using in vitro virulence assays. Effect of carvacrol on the virulence factors was
also studied.
Eugenol, methyl eugenol, carvacrol and thymol had antifungal activity against C. auris clinical
isolates. Carvacrol was the most active phenol with median MIC of 0.125 mg/ml and MFC of 0.25 mg/ml, and its combination with fluconazole, amphotericin B, nystatin and caspofungin
resulted synergistic and additive effects in 68%, 64%, 96% and 28% of the strains, respectively.
Combination also reduced the original MIC values of the drugs. All test strains showed
adherence ability to epithelial cells and 96% of strains showed strong proteinase activity. None
of the strains produced hyphae and phospholipase. Carvacrol at MIC value significantly
inhibited the proteinase production in C. auris (p<0.01), while at subinhibitory concentrations
(0.063 mg/ml) it significantly inhibited its adherence to epithelial cells (p<0.02).
This study showed that C. auris possess various virulence factors such as the ability to adhere
to epithelial cells and proteinase activity. Monoterpene phenols have antifungal activity against
this pathogen. Carvacrol has the most inhibitory effect. It also showed an enhanced antifungal
activity in combination with antifungal agents and anti-virulence activity against C. auris.
Therefore, it has potential to be developed into a novel antifungal agent
Description
Dissertation submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in fulfillment of the requirements for the degree of Master of Science in Medicine, 2020
Keywords
Citation
Shaban, Siham Ibrahim Ahmad (2020) Identification of virulence factors in Candida auris and antifungal activity of monoterpene phenols against this pathogen, University of the Witwatersrand, Johannesburg, <http://hdl.handle.net/10539/30472>