Biofilm inhibiting properties of compounds from the leaves of Warburgia ugandensis Sprague subsp ugandensis against Candida and staphylococcal biofilms

Abstract

Warburgia ugandensis Sprague subspecies ugandensis is a plant widely distributed in Eastern, Central and Southern Africa. In humans, it is used to treat respiratory infections, tooth aches, malaria, skin infections, venereal diseases, diarrhea, fevers and aches. Aim of the studyThis study aims to identify the bioactive compounds against clinically important biofilm-forming strains of Candida and staphylococci that are responsible for tissue and implanted device-related infections. MethodsUsing a bioassay-guided fractionation approach, hexane -, ethanol -, acetone -and water extracts from the leaves of W. ugandensis, their subsequent fractions and isolated compounds were tested against both developing and preformed 24h-biofilms of Candida albicans SC5314, Candida glabrata BG2 Candida glabrata ATCC 2001, Staphylococcus epidermidis 1457 and Staphylococcus aureus USA 300 using microtiter susceptibility tests. Planktonic cells were also tested in parallel for comparison purposes. Confocal scanning laser microscopy was also used to visualize effects of isolated compounds on biofilm formation. ResultsWarburganal, polygodial and alpha-linolenic acid (ALA) were the major bioactive compounds isolated from the acetone extract of W. ugandensis. For both warburganal and polygodial, the biofilm inhibitory concentration that inhibits 50% of C. albicans developing biofilms (BIC 50 ) was 4.5±1 and 10.8±5 μg/mL respectively. Against S. aureus developing biofilms, this value was 37.9±8 μg/mL and 25 μg/mL with warburganal and ALA respectively. Eradication of preformed h biofilms was also observed. Interestingly, synergy between the sesquiterpenoids and azoles against developing C. albicans biofilms resulted in an approximately ten-fold decrease of the effective concentration required to completely inhibit growth of the biofilms by individual compounds. The hydroxyl group in position C-9 in warburganal was identified as essential for activity against staphylococcal biofilms. We also identified additional promising bioactive sesquiterpenoids; drimenol and drimendiol from the structure-activity relationship (SAR) studies. ConclusionsALA and four sesquiterpenoids: polygodial, warburganal, drimenol and drimendiol, have shown biofilm-inhibitory activity that has not been reported before and is worth following up. These compounds are potential drug candidates to manage biofilm-based infections, possibly in combination with azoles.

Plant Preparations and Compounds with Activities against Biofilms Formed by Candida spp.

“…According to the European Committee on Antimicrobial Susceptibility Testing (EUCAST), the antifungal clinical breakpoints are between 0.001 mg/L and 16 mg/L [ 60 ]. Using EUCAST guidelines in this review, the most active compounds that inhibit (>50%) Candida biofilm formation are lichochalcone A (from 0.2 mg/L) [ 61 ], thymol (from 3.12 mg/L) [ 26 ], dioscin (from 3.9 mg/L) [ 31 ], baicalein (from 4 mg/L) [ 62 ], warburganal (4.5 mg/L) [ 52 ], pterostilbene, waltheriones and riccardin D (both from 8 mg/L) [ 63 , 64 , 65 ], polygodial (10.8 mg/L) [ 52 ], cannabidiol and eugenol (both from 12.5 mg/L) [ 58 , 66 ], and ivalin (15.4 mg/L) [ 67 ]. It is interesting that monotherpenes, which represent the highest percentage of substances listed in Table 2 , are not the most active compounds.…”

Fungal Biofilms as a Valuable Target for the Discovery of Natural Products That Cope with the Resistance of Medically Important Fungi—Latest Findings

“…In the same year, Lemos et al [ 159 ] demonstrated that Sc, at its MIC (50 µg/mL), was able to reduce the preformed biofilms of a resistant C. tropicalis strain in 68.2%, and to inhibit the biofilm formation. Kipanga et al [ 160 ] showed that the drimane sesquiterpene dialdehydes warburganal and polygodial, obtained from Warburgia ugandensis Sprague (Canellaceae), inhibited C. albicans biofilm formation with MBIC 50 of 4.5 and 10.8 µg/mL, respectively, and with MBIC 50 of 49.1 and 50.6 µg/mL, respectively, against C. glabrata . Regarding biofilm eradication, warburganal and polygodial showed MBEC 50 of 16.4 and 16.0 µg/ml, respectively, against C. albicans but did not inhibit C. glabrata biofilm eradication.…”

Investigating the Antifungal Mechanism of Action of Polygodial by Phenotypic Screening in Saccharomyces cerevisiae

“…Apart from the anti-feedant activity against a number of pests [ 1 , 2 , 3 ], polygodial ( Figure 1 ) has been reported to possess biological activities such as antifungal [ 4 , 5 , 6 ], antibacterial [ 7 ], anti-tumor [ 8 ], larvicidal [ 9 ], antihelminthic [ 10 ], antifouling [ 11 ], anti-inflammatory [ 12 ], analgesic [ 13 ], antitrypanosomal, and antileishmanial activities [ 14 ]. As a bioactive constituent, it is produced in several plants of the Canellaceae [ 1 ], Polygonaceae [ 15 ], and Winteraceae [ 16 ] families, as well as in marine animals such as sponges and molluscs [ 17 , 18 ].…”

“…As a bioactive constituent, it is produced in several plants of the Canellaceae [ 1 ], Polygonaceae [ 15 ], and Winteraceae [ 16 ] families, as well as in marine animals such as sponges and molluscs [ 17 , 18 ]. Recently, we isolated polygodial from Warburgia ugandensis Sprague subspecies ugandensis (Canellaceae) and showed its activity against Candida albicans [ 6 ]. Specifically, we showed that low concentrations of polygodial are not only active against the planktonic forms of C. albicans , but that the compound is also active against its biofilm forms (biofilm inhibiting concentration: BIC 50 =10.8 ± 5 μg/mL); which are a major menace to public health due to their increased resistance to currently available antifungals [ 19 ].…”