Simple Carbohydrate Derivatives Diminish the Formation of Biofilm of the Pathogenic Yeast Candida albicans

Abstract

The opportunistic human fungal pathogen Candida albicans relies on cell morphological transitions to develop biofilm and invade the host. In the current study, we developed new regulatory molecules, which inhibit the morphological transition of C. albicans from yeast-form cells to cells forming hyphae. These compounds, benzyl α-l-fucopyranoside and benzyl β-d-xylopyranoside, inhibit the hyphae formation and adhesion of C. albicans to a polystyrene surface, resulting in a reduced biofilm formation. The addition of cAMP to cells treated with α-l-fucopyranoside restored the yeast-hyphae switch and the biofilm level to that of the untreated control. In the β-d-xylopyranoside treated cells, the biofilm level was only partially restored by the addition of cAMP, and these cells remained mainly as yeast-form cells.Antibiotics 2020, 9, 10 2 of 11 system. For example, the hyphal glucan consists of a unique cyclic (1-3)-linked polymer backbone with long (1-6)-linked side chains [22]. Hyphae also have less mannan, compared to yeast-form cells [23]. The morphological transition from yeast-form cells to hyphae (i.e., switching) is a complex, tightly regulated process during the biofilm maturation, which is regulated by environmental conditions and quorum sensing molecules such as farnesol and tyrosol [21]. Multiple signaling pathways such as cyclic adenosine monophosphate/protein kinase A (cAMP-PKA), high-osmolarity glycerol (HOG), mitogen-activated protein kinases (MAPK), and several transcriptional factors, Efg1, Bcr1, Ndt80, Cph1, Cph2, Tec1, Nrg1, Rfg1, and Tup1 are known to regulate the morphological transition and hyphal adhesion [1,21,[24][25][26]. Upon stimuli favoring hyphae, the yeast cells produce a germ tube that extends by polarized growth by the activity of membrane-bound vesicles supplying the components of the plasma membrane and cell wall to the growing hyphae [21].Different carbohydrates have been explored for their possibilities to disturb or prevent adhesion, biofilm formation, and the extension of an already existing biofilm of C. albicans [27][28][29][30][31][32][33][34]. In addition, some natural products of plant origin were recently shown to reduce the adhesion of C. albicans and its biofilm formation by inhibiting the yeast-to-hyphae transition [35,36].In this study, we synthesized and tested the effect of simple monosaccharides and glycosides (Chart 1) on C. albicans biofilm development on polystyrene surfaces.

Deciphering the molecular components of the quorum sensing system in the fungus Ophiostoma piceae

“…Cell-membrane variations were expected as morphological transition was already observable 22 h after inoculation. Together with cell membrane, cell wall was also expected to vary as a result of changes in ergosterol, chitin, β1–3 and β1–6 glucans biosynthesis ( 52 ).…”

Synergy of R-(–)carvone and cyclohexenone-based carbasugar precursors with antibiotics to enhance antibiotic potency and inhibit biofilm formation

“…Various classes of substances with anti-biofilm properties have already been identified and tested for their suitability to inhibit biofilm, such as carbohydrate derivatives (e.g. derivatives of α- d -mannoside 10 , fucose or xylose 33 ), d -amino acids 34 , polysaccharides (e.g. group II capsular polysaccharides 35 , chitosan derivatives 36 ) or antimicrobial peptides 37 .…”

A novel non-antimicrobial treatment of bacterial vaginosis: An open label two-private centre study

“…pHyph, a vaginal pessary, containing glucono-delta-lactone (GDL) and sodium gluconate (NaG), disrupts biofilm formation and restores normal pH [16]. GDL and NaG are both accepted as safe food additives, and suitable for use in clinical testing and have been formulated as the "pHyph" slow-release vaginal pessary ( Figure 1) [16]. In contact with the vaginal fluid they are hydrolysed to gluconic acid, which is weakly acidic, thereby restoring the vaginal pH to normal.…”

“…This inhibits the growth of Gardnerella vaginalis. GDL disrupts the biofilm both via provision of alternative carbohydrate sources, which diminish biofilm formation, and by a direct disruptive effect via reduced vaginal pH [16].…”