Inhibition of Candida albicans Biofilm Formation by Farnesol, a Quorum-Sensing Molecule

Abstract

Farnesol is a quorum-sensing molecule that inhibits filamentation in Candida albicans. Both filamentation and quorum sensing are deemed to be important factors in C. albicans biofilm development. Here we examined the effect of farnesol on C. albicans biofilm formation. C. albicans adherent cell populations (after 0, 1, 2, and 4 h of adherence) and preformed biofilms (24 h) were treated with various concentrations of farnesol (0, 3, 30, and 300 M) and incubated at 37°C for 24 h. The extent and characteristics of biofilm formation were then assessed microscopically and with a semiquantitative colorimetric technique based on the use of 2,3-bis(2-methoxy-4-nitro-5-sulfo-phenyl)-2H-tetrazolium-5-carboxanilide. The results indicated that the effect of farnesol was dependent on the concentration of this compound and the initial adherence time, and preincubation with 300 M farnesol completely inhibited biofilm formation. Supernatant media recovered from mature biofilms inhibited the ability of planktonic C. albicans to form filaments, indicating that a morphogenetic autoregulatory compound is produced in situ in biofilms. Northern blot analysis of RNA extracted from cells in biofilms indicated that the levels of expression of HWP1, encoding a hypha-specific wall protein, were decreased in farnesol-treated biofilms compared to the levels in controls. Our results indicate that farnesol acts as a naturally occurring quorum-sensing molecule which inhibits biofilm formation, and we discuss its potential for further development and use as a novel therapeutic agent. Candida albicans is the most frequently isolated human fungal pathogen (5). The most recent surveys have shown thatCandida is the third or fourth most commonly isolated bloodstream pathogen in United States hospitals, having surpassed gram-negative rods in frequency (2,13,20,21). Notably, yeasts (mainly C. albicans) are the third leading cause of catheterrelated infections, and they have the second highest colonization to infection rate and the highest crude mortality rate overall (8,22).Structured microbial communities attached to surfaces, commonly referred to as biofilms, have increasingly been found to be sources of infection by C. albicans, especially in view of the vast number of biomaterials that are now being used in the medical industry. Biomaterials, such as stents, catheters, and orthopedic joints, for example, serve as excellent substrates for microbial adhesion and subsequent biofilm formation (6, 10, 15). Biofilms are specific and organized communities of cells under the control of signaling molecules rather than random accumulations of cells resulting from cell division (9). Cell-cell signaling, particularly quorum sensing, has been the focus of much research over the past decade in the microbiological arena. It has been demonstrated that quorum-sensing molecules are essential for bacterial biofilm formation and that homoserine lactones act in a concentrationdependent manner; a threshold concentration triggers the formation of a biofilm (17,27). Rece...

Chemical profiling of Elaeocarpus serratus L. by GC-MS

“…It is also used as a deodorant in cosmetic products because of its anti-bacterial activity [16] . The anti-fungal activity of farnesol has also been reported [17] . Citronellyl isobutyrate is an ester of propanoic acid which is widely used as flavoring agent and is known to possess insect repellent and antimicrobial properties [18][19][20] .…”

(1‐aryloxy‐2‐hydroxypropyl)‐phenylpiperazine derivatives suppress Candida albicans virulence by interfering with morphological transition

“…However, problems such as selectivity, toxicity and the development of resistance have led to an emergent need for new strategies and novel drugs to efficiently treat C. albicans infections (Chandra et al ., 2001; Ramage et al ., 2002; Tobudic et al ., 2010). Several categories of natural products and synthetic chemicals have been screened and evaluated for their efficacy against C. albicans adhesion and morphological transition in recent years.…”

Influence of heterocyclic and oxime-containing farnesol analogs on quorum sensing and pathogenicity in Candida albicans

“…12 The analogs also provide a means of establishing differences and similarities between farnesol's effect on virulence and its ability to block both hyphal development and biofilm formation. [3] and [29] Along these lines, it is interesting to note that an analog of triazole 10 bearing five additional carbons has been reported to be a potent activator of protein kinase C. 20 Of course, the differences in the pathogenicity of C. albicans observed in the presence of farnesol, 5, and 10 could also be due to differing pharmacokinetics or their differing influence on mouse cytokine production.…”