Abstract
Candida albicans is an opportunistic pathogen causes fungal infections that range from common skin infections to persistent infections through biofilm formation on tissues, implants and life threatening systemic infections. New antifungal agents or therapeutic methods are desired due to high incidence of infections and emergence of drug-resistant strains. The present study aimed to evaluate (i) the antifungal and antibiofilm activity of 1-alklyl-3-methyl imidazolium ionic liquids ([CnMIM]+[X]–, n = 4, 12 and 16) against Candida albicans ATCC 10231 and two clinical C. albicans strains and (ii) the mechanism of action of promising antifungal ionic liquid on C. albicans. Two of the tested compounds were identified as more effective in preventing growth and biofilm formation. These ionic liquid compounds with –dodecyl and –hexadecyl alkyl groups effectively prevented biofilm formation by fluconazole resistant C. albicans 10231 and two other clinical C. albicans strains. Although both the compounds caused viability loss in mature C. albicans biofilms, an ionic liquid with –hexadecyl group ([C16MIM]+[Cl]–) was more effective in dispersing mature biofilms. This promising ionic liquid compound ([C16MIM]+[Cl]–) was chosen for determining the underlying mode of action on C. albicans cells. Light microscopy showed that ionic liquid treatment led to a significant reduction in cell volume and length. Increased cell membrane permeability in the ionic liquid treated C. albicans cells was evident in propidium iodide staining. Leakage of intracellular material was evident in terms of increased absorbance of supernatant and release of potassium and calcium ions into extracellular medium. A decrease in ergosterol content was evident when C. albicans cells were cultured in the presence of antifungal ionic liquid. 2′,7′-Dichlorodihydrofluorescein acetate assay revealed reactive oxygen species generation and accumulation in C. albicans cells upon treatment with antifungal ionic liquid. The effect of antifungal ionic liquid on mitochondria was evident by decreased membrane potential (measured by Rhodamine 123 assay) and loss of metabolic activity (measured by MTT assay). This study demonstrated that imidazolium ionic liquid compound exert antifungal and antibiofilm activity by affecting various cellular processes. Thus, imidazolium ionic liquids represent a promising antifungal treatment strategy in lieu of resistance development to common antifungal drugs.
Highlights
Fungal pathogens are a major health issue causing over 1.6 million deaths annually (Almeida et al, 2019)
The antifungal activity of three ionic liquids and antifungal drugs was expressed as MIC and MFC against C. albicans 10231 (Table 2)
The major challenges in developing new antifungal drugs or therapeutic strategies against Candida albicans are (i) its opportunistic pathogenicity causing both superficial and systemic fungal infections, (ii) its complex and polymorphic biofilm structure, and (iii) emergence of resistance in C. albicans strains against antifungal drugs like fluconazole
Summary
Fungal pathogens are a major health issue causing over 1.6 million deaths annually (Almeida et al, 2019). Several species of Candida are responsible for the fungal infections, collectively called as candidiasis. These are commensal organisms in healthy individuals and reside in gastrointestinal, respiratory, and genitourinary tracts. About 50 to 70% of systemic fungal infections are caused by Candida spp. Persistent Candida infections are increasingly being reported in medically implanted devices such as catheters, heart valves, pacemakers, vascular bypass grafts, dentures and endotracheal tubes leading to high mortalities (Ramage et al, 2006; Sardi et al, 2013; Santos et al, 2018). Biofilm mode of growth by Candida spp. further complicates the treatment as the cells reside in biofilms are about 2000 times more resistant to fluconazole and amphotericin B over their planktonic counterparts (Bergamo et al, 2015)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
