Candida and anti-candidal plant compounds: History
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Subjects: Plant Sciences
Contributor:
Tomasz M. Karpinski

Fungi from the genus Candida are very important human and animal pathogens. Many strains can produce biofilms, which inhibit the activity of antifungal drugs and increase the tolerance or resistance to them as well. 

  • Candida
  • biofilm
  • treatment
  • antifungals
  • natural compounds
  • essential oil
  • extract
  • minimal inhibitory concentration (MIC)

1. Introduction

The genus Candida contains about 150 species; however, most are environmental organisms. The most medically important is Candida albicans, which accounts for about 80% of infections. C. albicans causes more than 400,000 cases of bloodstream life-threatening infections annually, with a mortality rate of about 42% [1]. Candida non-albicans species that are mainly responsible for infections are C. glabrata, C. parapsilosis, C. tropicalis, C. krusei, and C. dubliniensis [2]. Less frequently identified are C. guilliermondii, C. lusitaniae, C. rugosa, C. orthopsilosis, C. metapsilosis, C. famata, C. inconspicua, and C. kefyr [3].
C. albicans is a member of the commensal microflora. It colonizes the oral mucosal surface of 30–50% of healthy people. The rate of carriage increases with age and in persons with dental prostheses up to 60% [4][5][6]. Opportunistic infection caused by Candida species is termed candidiasis. At least one episode of vulvovaginal candidiasis (or thrush) concerns 50 to 75% of women of childbearing age [7]. Candidiasis can also affect the oral cavity, penis, skin, nails, cornea, and other parts of the body. In immunocompromised persons, untreated candidiasis poses the risk of systemic infection and fungemia [5][8]. Candida can be an important etiological factor in the infection of chronic wounds that are difficult to treat; this is mainly related to the production of biofilm [9].
Treatment of candidiasis depends on the infection site and the patient’s condition. According to guidelines, vulvovaginal candidiasis should be treated with oral or topical fluconazole; however, regarding C. glabrata infection, topical boric acid, nystatin, or flucytosine is suggested. In oropharyngeal candidiasis, the treatment options include clotrimazole, miconazole, or nystatin, and in severe disease, fluconazole or voriconazole. In candidemia and invasive candidiasis, the drugs of choice are echinocandins (caspofungin, micafungin, anidulafungin), fluconazole, or voriconazole; in resistant strains, amphoteticin B is used. In selected cases of candidemia caused by C. krusei, voriconazole is recommended [10][11][12]. More details can be found in the Guidelines of the Infectious Diseases Society of America [12] and the European Society of Clinical Microbiology and Infectious Diseases [11]. Increasingly, Candida species are becoming resistant to drugs. Marak and Dhanashree [13] tested the resistance of 90 Candida strains isolated from different clinical samples, such as pus, urine, blood, and body fluid. Their study revealed that about 41% of C. albicans strains are resistant to fluconazole and voriconazole. Simultaneously, about 41% of C. tropicalis strains are resistant to voriconazole and about 36% of strains to fluconazole. In strains of C. krusei, about 23% are resistant to fluconazole and about 18% to voriconazole. Rudramurthy et al. [14] studied resistance in C. auris, which is considered a multiresistant pathogen. Among 74 strains obtained from patients with candidemia, over 90% of strains were resistant to fluconazole and about 73% to voriconazole. Virulence factors of Candida species include the secretion of hydrolases, the transition of yeast to hyphae, phenotypic switching, and biofilm formation [15][16]. All microorganisms in biofilm form are more resistant to antimicrobial and host factors, which leads to difficulties in eradication [17]. It has also been shown that resistance to drugs increases significantly in the case of Candida biofilm occurrence. Biofilm prevents the spread of antifungals; moreover, fluconazole is bound by the biofilm matrix [18]. The formation of a Candida biofilm during infection increases mortality, length of hospital stay, and cost of antifungal therapy [19].

2. Plant Preparations That Display Activity against Candida Biofilms

The present review includes 60 articles in which Candida biofilm formation was inhibited by at least 50%. It has been shown that preparations from 34 plants demonstrate activity against Candida biofilms. Among them were 29 essential oils and 16 extracts. The plants from the following families dominated: Lamiaceae (6 species in 5 genera), Myrtaceae (5 species in 4 genera), Asteraceae (4 species in 4 genera), Fabaceae (4 species in 3 genera), and Apiacae (4 species in 2 genera).
Plants from the Lamiaceae family had the best antifungal activity, including Lavandula dentata (0.045–0.07 mg/L) [20], Satureja macrosiphon (0.06–8 mg/L) [21], and Ziziphora tenuior (2.5 mg/L) [22]. Artemisia judaica (2.5 mg/L) from the Asteraceae family [23], Lawsonia inermis (2.5–12.5 mg/L) from the Lythraceae family [24], and Thymus vulgaris (12.5 mg/L) from the Lamiaceae family [25] likewise exhibited good antifungal activity (Table 1). All preparations were essential oils, with the exception of Lawsonia inermis, which was an extract. Most of the plant preparations presented in Table 1 acted on biofilm formation and/or mature biofilms.
Table 1. Antifungal (MICs) and anti-biofilm (inhibition >50%) activity of plant preparations (essential oils or extracts).
Name of Plant
(Family)		 Main Compounds Presented in the Reference
(EO: Essential Oil)		 Targeted Species of Candida MICs
(mg/L; mL/L)		 Inhibition of Biofilm Formation by at Least 50% (mg/L; mL/L) Inhibited Stage of Biofilm; Method of Biofilm Detection Ref.
Acorus calamus var. angustatus Besser = A. tatarinowii Schott
(Acoraceae)		 EO: asaraldehyde, 1-(2,4,5-trimethoxyphenyl)-1,2-propanediol, α-asarone, β-asarone, γ-asarone,
acotatarone C		 C. albicans 51.2 50–200 Mature biofilm; crystal violet and fluorescence microscopy [26]
Allium sativum L.
(Amaryllidaceae)		 Extract: allicin C. albicans 400 60 Biofilm formation; XTT [27]
Aloysia gratissima (Aff & Hook).Tr
(Verbenaceae)		 EO: E-pinocamphone (16.07%), β-pinene (12.01%), guaiol (8.53%), E-pinocarveol acetate (8.19%) C. albicans 15 500 Biofilm formation; crystal violet [28]
Artemisia judaica L.
(Asteraceae)		 EO: piperitone (30.4%), camphor (16.1%), ethyl cinnamate (11.0%), chrysanthenone (6.7%) C. albicans 1.25 2.5 Mature biofilm; XTT [23]
C. guillermondii 1.25 2.5
C. krusei 1.25 2.5
C. parapsilosis 1.25 2.5
C. tropicalis 1.25 2.5
Buchenavia tomentosa Eichler
(Combretaceae)		 Extract: gallic acid, kaempferol, epicatechin, ellagic acid, vitexin, and corilagin C. albicans 625 312.5 Biofilm formation and mature biofilm; culture [29]
Chamaecostus cuspidatus (Nees & Mart.) C.Specht & D.W.Stev.
(Costaceae)		 Extract: dioscin,
aferoside A, aferoside C		 C. albicans 250 15.62 Biofilm formation and mature biofilm; MTT [30]
Cinnamomum verum J. Presl
(Lauraceae)		 EO: eugenol (77.22%), benzyl benzoate (4.53%), trans-caryophyllene (3.39%), acetyl eugenol (2.75%), linalool 2.11% C. albicans 1000 150 Biofilm adhesion; XTT [31]
C. dubliniensis 1000 200
C. tropicalis 1000 350
Citrus limon (L.) Osbeck
(Rutaceae)		 EO: limonene (53.4%), neral (11%), geraniol (9%), trans-limonene oxide (7%), nerol (6%) C. albicans 500 2000 Biofilm formation and mature biofilm; XTT [32]
C. glabrata 250 1000
C. krusei 500 125
C. orthopsilosis 500 1000
C. parapsilosis 500 2000
C. tropicalis 250 2000
Copaifera paupera (Herzog) Dwyer
(Fabaceae)		 Extract: galloylquinic acids, quercetrin, afzelin C. glabrata 5.89 46.87 Biofilm formation and mature biofilm; XTT [33]
Copaifera reticulata Ducke
(Fabaceae)		 Extract: galloylquinic acids, quercetrin, afzelin C. glabrata 5.89 46.87 Biofilm formation and mature biofilm; XTT [33]
Coriandrum sativum L.
(Apiaceae)		 EO: 1-decanol (33.91%), E-2-decen-1-ol (23.59%), 2-dodecen-1-ol (13.06%), E-2-tetradecen-1-ol (5.46%) C. albicans 7 250 Biofilm formation; crystal violet [28]
EO: decanal (19.09%), trans-2-decenal (17.54%), 2-decen-1-ol (12.33%), cyclodecane (12.15%) C. albicans 15.6 62.5–125 Biofilm adhesion; crystal violet [34]
C. dubliniensis 31.2 62.5–125
C. rugosa 15.6 62.5
C. tropicalis 31.2 31.25–250
Croton eluteria (L.) W.Wright
(Euphorbiaceae)		 EO: α-pinene (29.37%), β-pinene (19.35%), camphene (10.31%), 1,8-cineole (9.68%) C. albicans 4000 5–500 Biofilm formation; confocal laser microscopy [35]
Cupressus sempervirens L.
(Cupressaceae)		 EO: sabinene (20.3%), citral (20%), terpinene-4-ol (15.4%), α-pinene (8%) C. albicans 250 1000 Biofilm formation and mature biofilm; XTT [32]
C. glabrata 31.25 250
C. krusei 62.5 62.5
C. orthopsilosis 31.25 125
C. parapsilosis 62.5 500
C. tropicalis 250 500
Cymbopogon citratus (DC.) Stapf
(Poaceae)		 EO: no composition C. albicans 180–360 22.5–180 Biofilm formation; XTT [36]
Cymbopogon martini (Roxb.) W.Watson
(Poaceae)		 EO: no composition C. albicans 16,800 800 Biofilm formation; XTT [37]
Cymbopogon nardus (L.) Rendle
(Poaceae)		 EO: citronellal (27.87%),
geraniol (22.77%), geranial (14.54%), citronellol (11.85%), neral (11.21%)		 C. albicans 1000 2500–5000 Biofilm adhesion; XTT [38]
C. krusei 250–500 2500
C. parapsilosis 500–1000 5000–10,000
Cyperus articulatus L.
(Cyperaceae)		 EO: α-pinene (5.72%), mustakone (5.66%), α-bulnesene (5.02%), α-copaene (4.97%) C. albicans 125 250 Biofilm formation; crystal violet [28]
Eucalyptus sp.
(Myrtaceae)		 EO: no composition C. albicans 8 8 Mature biofilm; luminescence [39]
Eucalyptus globulus Labill.
(Myrtaceae)		 EO: 1,8-cineole (75.8%), p-cymene (7.5%), α-pinene (7.4%), limonene (6.4%) C. albicans 219 11,250–22,500 Mature biofilm; atomic force microscopy [40]
C. glabrata 219 11,250–22,500
C. tropicalis 885 11,250–22,500
EO: no composition C. albicans 8400 500 Biofilm formation; XTT [37]
Eugenia brasiliensis Lam. (Myrtaceae) Extract: no composition C. albicans 15.62–31.25 156 Mature biofilm; scanning electron microscopy [41]
Eugenia leitonii Legrand nom. inval.
(Myrtaceae)		 Extract: no composition C. albicans 15.62–250 156 Mature biofilm; scanning electron microscopy [41]
Helichrysum italicum (Roth) G.Don
(Asteraceae)		 EO: α-pinene (27.64%), γ-elemene (23.84%), β-caryophyllene (13.05%), α-longipinene (11.25%) C. albicans 6000 10–500 Biofilm formation; confocal laser microscopy [35]
Laserpitium latifolium L.
(Apiaceae)		 Extract: laserpitine C. albicans 1250 6300 Mature biofilm; luminescence [42]
C. krusei 1250 6300
Laserpitium ochridanum Micevski
(Apiaceae)		 Extract: isomontanolide,
montanolide, tarolide		 C. albicans 5000 10,000 Mature biofilm; luminescence [42]
C. krusei 5000 10,000
Laserpitium zernyi Hayek = L. siler subsp. zernyi (Hayek) Tutin
(Apiaceae)		 Extract: isomontanolide,
montanolide, tarolide		 C. albicans 7500 15,000 Mature biofilm; luminescence [42]
C. krusei 7500 37,500
Lavandula dentata L.
(Lamiaceae)		 EO: eucalyptol (42.66%), β-pinene (8.59%), trans-α-bisabolene (6.34%), pinocarveol (6.3%) C. albicans 0.15–0.18 0.045–0.07 Mature biofilm; XTT [20]
Lawsonia inermis L.
(Lythraceae)		 Extract: no composition C. albicans 10 2.5–12.5 Mature biofilm; MTT [24]
Lippia sidoides Cham.
(Verbenaceae)		 EO: thymol (65.76%), p-cymene (17.28%), α-caryophyllene (10.46%), cyclohexanone (6.5%) C. albicans 250 500 Biofilm formation; crystal violet [28]
Litsea cubeba (Lour.) Pers.
(Lauraceae)		 EO: limonene (37%), neral (31.4%), citral (12%), linalool (4%) C. albicans 500 2000 Biofilm formation and mature biofilm; XTT [32]
C. glabrata 250 2000
C. krusei 62.5 250
C. orthopsilosis 250 2000
C. parapsilosis 500 1000
C. tropicalis 1000 2000
Mentha × piperita L.
(Lamiaceae)		 EO: menthol (32.93%), menthone (24.41%), 1,8-cineole (7.89%) C. albicans 1–10 10 Biofilm formation; MTT [43]
EO: no composition C. albicans 11,600 800 Biofilm formation; XTT [37]
Mikania glomerata Spreng
(Asteraceae)		 EO: germacrene D (38.29%), α-caryophyllene (9.49%), bicyclogermacrene (7.98%), caryophyllene oxide (4.28%) C. albicans 250 500 Biofilm formation; crystal violet [28]
Myrtus communis L.
(Myrtaceae)		 EO: α-pinene (39.8%), 1,8-cineole (24.8%), limonene (10.7%), linalool (6.4%) C. albicans 1250–10,000 None or 1250 No data; no data [44]
C. parapsilosis 1250 to >16,000 1250
C. tropicalis 1250–16,000 1250
Ononis spinosa L.
(Fabaceae)		 Extract: kaempherol-O-dihexoside, kaempherol-O-hexoside-pentoside, kaempherol-O-hexoside, quercetin-O-hexoside-pentoside, acetylquercetin-O-hexoside C. albicans 620 10,000 Mature biofilm; luminescence [45]
C. krusei 620 5000
C. tropicalis 310 10,000
Pelargonium graveolens L’Hér.
(Geraniaceae)		 EO: geraniol (42.3%), linalool (20.1%), citronellol (11.1%), menthone (8.0%) C. albicans 125 4000–8000 Mature biofilm; XTT [46]
Piper claussenianum (Miq.) C. DC.
(Piperaceae)		 EO: nerolidols C. albicans 4100–9600 2400–12,600 Mature biofilm; MTT [47]
Portulaca oleracea L.
(Portulacaceae)		 Extract: no composition C. albicans 10 12.5 Mature biofilm; MTT [24]
Punica granatum L.
(Lythraceae)		 Extract: ellagic acid C. albicans 1000 100–750 Biofilm formation and mature biofilm; crystal violet [48]
Santolina impressa Hoffmanns. & Link
(Asteraceae)		 EO: β-pinene (22.5%), 1,8-cineole (10.0%), limonene (9.1%), camphor (8.1%), β-phellandrene (8.0%) C. albicans 540 70–1050 Biofilm formation; XTT [49]
Satureja hortensis L.
(Lamiaceae)		 EO: thymol (45.9%),
gamma-terpinen (16.71%), carvacrol (12.81%), p-cymene (9.61%)		 C. albicans 200–400 400–4800 Biofilm adhesion, formation, and mature biofilm; MTT [50]
Satureja macrosiphon (Coss.) = Micromeria macrosiphon Coss.
(Lamiaceae)		 EO: linalool (28.46%), borneol (16.22%), terpinene-4-ol (14.58%), cis-sabinene hydrate (12.96%) C. albicans 0.06–4 0.06–8 Biofilm formation; XTT [21]
C. dubliniensis 0.25–4 2–8
Syzygium aromaticum (L.) Merr. & L.M.Perry = Eugenia caryophyllus (Spreng.) Bullock & S.G.Harrison
(Myrtaceae)		 EO: no composition C. albicans 100–200 50 Biofilm formation; XTT [36]
EO: no composition C. albicans 48,000 3300 Biofilm formation; XTT [37]
Thymus vulgaris L.
(Lamiaceae)		 EO: thymol (54.73%), carvacrol (12.42%), terpineol (4.00%), nerol acetate (2.86%), fenchol (0.5%) C. albicans 1.56–25 12.5 Biofilm formation; absorbance, crystal violet, and scanning electron microscopy [25]
C. tropicalis 25–50 12.5
Warburgia ugandensis Sprague
(Canellaceae)		 Extract: ugandenial A, warburganal, polygodial, alpha-linolenic acid ALA C. albicans Lack of data 1000 Biofilm formation and mature biofilm; XTT and confocal laser microscopy [51]
C. glabrata Lack of data 1000
Ziziphora tenuior L.
(Lamiaceae)		 EO: pulegone (46.8%),
p-menth-3-en-8-ol (12.5%),
isomenthone (6.6%),
8-hydroxymenthone (6.2%),
isomenthol (4.7%)		 C. albicans 1.25 2.5 Mature biofilm; XTT [22]
Zuccagnia punctata L.
(Fabaceae)		 Extract: no composition C. albicans 400 100 Biofilm formation and mature biofilm; XTT and crystal violet [52]
Legend: MIC—minimal inhibitory concentration; XTT—reduction assay of 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[carbonyl(phenylamino)]-2H-tetrazolium hydroxide; MTT—reduction assay of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide [53][54].

3. Plant Compounds That Display Activity against Candida Biofilm

It has been shown that 69 compounds obtained from plants demonstrate activity against Candida biofilms (Table 2). Among these, the most common are monotherpenes (20), followed by sesquiterpene lactones (7) and sesquiterpenes (6). Another big group is also phenolic compounds, including phenols (6), phenolic acids (5), phenolic aldehydes (2), polyphenols (2), and phenolic alcohol (1).
Table 2. Antifungal and antibiofilm activity of plant compounds.
Active Compound Example of Plant Origin Targeted Fungus MICs
(mg/L, mL/L)		 Inhibition of Biofilm Formation by at Least 50% (mg/L, mL/L) Inhibited Stage of Biofilm; Method of Biofilm Detection Ref.
Antidesmone
(alkaloid)		 Waltheria indica,
W. brachypetala		 C. albicans 32 16 Mature biofilm; XTT [55]
C. glabrata >32 16
C. krusei 16 16
C. parapsilosis 4 16
C. tropicalis >32 16
Anisaldehyde
(phenolic aldehyde)		 Pimpinella anisum ,
Foeniculum vulgare		 C. albicans 500 500 Mature biofilm; XTT, crystal violet, and inverted light microscopy [56]
Anisic acid
(phenolic acid)		 Pimpinella anisum C. albicans 4000 4000 Mature biofilm; XTT, crystal violet, and inverted light microscopy [56]
Anisyl alcohol
(phenolic alcohol)		 Pimpinella anisum C. albicans 31 500 Mature biofilm; XTT, crystal violet, and inverted light microscopy [56]
Baicalein
(flavonoid)		 Scutellaria baicalensis,
S. lateriflora		 C. albicans No data 4–32 Biofilm formation; XTT [57]
Camphene
(monotherpene)		 Croton eluteria,
Cinnamomum verum		 C. albicans No data 500 Biofilm formation; confocal laser microscopy [35]
C. albicans 1000 2000 Mature biofilm; XTT, crystal violet, and inverted light microscopy [58]
Camphor
(bicyclic monotherpene)		 Cinnamomum camphora,
Artemisia annua		 C. albicans 125–250 Not or 62.5–250 Biofilm formation; crystal violet and absorbance [59]
C. glabrata 175 Not
C. krusei 350 Not
C. parapsilosis 125 Not
C. tropicalis 175 175
Cannabidiol
(cannabinoid)		 Cannabis sativa C. albicans No data 12.5–100 Biofilm formation; confocal microscopy [60]
Carvacrol
(phenol)		 Thymus serpyllum,
Carum carvi,
Origanum vulgare		 C. albicans 250 500 Mature biofilm; XTT, crystal violet, and inverted light microscopy [58]
100–20,000 300–1250 Mature biofilm; XTT [61]
1000 750–1500 Biofilm formation; MTT [62]
C. glabrata 100–20,000 300–1250 Mature biofilm; XTT [61]
C. parapsilosis 100–20,000 300–1250
Carvene/Limonene
(monotherpene)		 Citrus × aurantium,
Citrus limon		 C. albicans 1000 4000 Mature biofilm; XTT, crystal violet, and inverted light microscopy [58]
Carvone/Carvol
(monotherpene)		 Carum carvi,
Mentha spicata		 C. albicans >4000 250 Mature biofilm; XTT, crystal violet, and inverted light microscopy [58]
β-Caryophyllene
(sesquiterpene)		 Helichrysum italicum,
Caryophyllusaromaticus		 C. albicans No data 100–500 Biofilm formation; confocal laser microscopy [35]
1,4-Cineole
(monotherpene)		 Rosmarinus officinalis ,
Thymus vulgaris		 C. albicans >4000 4000 Mature biofilm; XTT, crystal violet, and inverted light microscopy [58]
1,8-Cineole/Eucalyptol
(monotherpene)		 Eucalyptus globulus,
Salvia officinalis,
Pinus sylvestris		 C. albicans 4000 4000 Mature biofilm; XTT, crystal violet, and inverted light microscopy [58]
8 4 Mature biofilm; luminescence [39]
3000–23,000 Not or 3000–23,000 Biofilm formation; crystal violet and absorbance [59]
C. glabrata 2000 Not
C. krusei 4000 2000–4000
C. parapsilosis 2000 1000–2000
C. tropicalis 4000 2000–4000
Cinnamaldehyde
(aldehyde)		 Cinnamomum sp.,
Apium graveolens		 C. albicans 62 125 Mature biofilm; XTT, crystal violet, and inverted light microscopy [56]
50–400 25–200 Mature biofilm; XTT [63]
Cinnamic acid
(phenolic acid)		 Cinnamomum sp. C. albicans 2000 4000 Mature biofilm; XTT, crystal violet, and inverted light microscopy [56]
Citral
(monotherpene)		 Melissa officinalis,
Backhousia citriodora		 C. albicans 500 1000 Mature biofilm; XTT, crystal violet, and inverted light microscopy [58]
Citronellal
(monotherpene)		 Cymbopogon citratus ,
Melissa officinalis		 C. albicans 500 1000 Mature biofilm; XTT, crystal violet, and inverted light microscopy [58]
β-Citronellol
(monotherpene)		 Melissa officinalis,
Pelargonium roseum		 C. albicans 500 1000 Mature biofilm; XTT, crystal violet, and inverted light microscopy [58]
Cuminaldehyde
(monotherpene)		 Carum carvi ,
Cinnamomum verum		 C. albicans 1000 to >4000 6000–7000 Biofilm formation; MTT [62]
p-Cymene
(monotherpene)		 Thymus vulgaris,
Eucalyptus sp.		 C. albicans 2000 4000 Mature biofilm; XTT, crystal violet, and inverted light microscopy [58]
8-Deoxoantidesmone
(alkaloid)		 Waltheria indica C. albicans 16 32 Mature biofilm; XTT [55]
C. glabrata >32 32
C. krusei 32 32
C. parapsilosis 32 32
C. tropicalis >32 32
2′,4′-Dihydroxy-3′-methoxychalcone
(chalcone)		 Zuccagnia punctata,
Oxytropis falcata		 C. albicans 100 25 Biofilm formation and mature biofilm; XTT and crystal violet [52]
Dioscin
(steroidal saponin)		 Dioscorea sp.,
Chamaecostus		 C. albicans 3.9–15.62 3.9–31.25 Biofilm formation and mature biofilm; MTT [30]
Ellagic acid
(polyphenol)		 Punica granatum L. C. albicans 75–100 25–40 Biofilm formation and mature biofilm; crystal violet [48]
Emodin
(anthraquinone)		 Rheum palmatum,
Frangula alnus		 C. albicans 12.5–50 Not or 100–400 Biofilm adhesion; MTT [64]
4α,5α-Epoxy-10α,14H-1-epi-inuviscolide
(sesquiterpene lactone)		 Carpesium macrocephalum C. albicans >128 38 Biofilm formation and mature biofilm; XTT [65]
Eugenol
(phenol)		 Syzygium aromaticum ,
Cinnamomum sp.		 C. albicans 50–400 12.5–200 Mature biofilm; XTT [63]
250 500 Mature biofilm; XTT, crystal violet, and inverted light microscopy [58]
500 500 Mature biofilm; XTT, crystal violet, and inverted light microscopy [56]
1200 10,000–80,000 Mature biofilm; XTT [66]
Farnesol
(sesquiterpene)		 Tilia sp.,
Cymbopogon sp.		 C. albicans 1000 500 Mature biofilm; XTT, crystal violet, and inverted light microscopy [56]
1000 500 Mature biofilm; XTT, crystal violet, and inverted light microscopy [58]
Gallic acid
(phenolic acid)		 Polygonum sp.,
Buchenavia tomentosa		 C. albicans 5000 2500 Biofilm formation and mature biofilm; culture [29]
Geraniol
(monotherpene)		 Pelargonium graveolens,
Rosa sp.		 C. albicans 1000 1000 Mature biofilm; XTT, crystal violet, and inverted light microscopy [58]
C. albicans 100–20,000 300–1250 Mature biofilm; XTT [61]
C. albicans No data 1000–8000 Mature biofilm; XTT [46]
C. glabrata 100–20,000 300–1250 Mature biofilm; XTT [61]
C. parapsilosis 100–20,000 300–1250
Guaiacol
(phenol)		 Guaiacum officinale ,
Apium graveolens		 C. albicans 500 1000 Mature biofilm; XTT, crystal violet, and inverted light microscopy [56]
Hydroxychavicol
(phenol)		 Piper betle C. albicans 125–500 125–1000 Biofilm formation and mature biofilm; XTT [67]
β-Ionone
(carotenoid)		 Lawsonia inermis ,
Camellia sinensis		 C. albicans 250 250 Mature biofilm; XTT, crystal violet, and inverted light microscopy [58]
Isomontanolide
(sesquiterpenic lactone)		 Laserpitium ochridanum,
L. zernyi		 C. albicans 50 250 Mature biofilm; luminescence [42]
C. krusei 200 250
Isopulegol
(monotherpene)		 Mentha rotundifolia,
Melissa officinalis		 C. albicans >4000 250 Mature biofilm; XTT, crystal violet, and inverted light microscopy [58]
Ivalin
(sesquiterpene lactone)		 Geigeria aspera,
Carpesium macrocephalum		 C. albicans >128 15.4 Biofilm formation and mature biofilm; XTT [65]
Laserpitine
(sesquiterpene lactone)		 Laserpitium latifolium,
Laserpitiumhalleri		 C. albicans 200 400 Mature biofilm; luminescence [42]
C. krusei 200 400
Lichochalcone A
(chalconoid)		 Glycyrrhiza sp. C. albicans 6.25–12.5 0.2–20 Biofilm formation; crystal violet [68]
Linalool
(monotherpene)		 Lavandula officinalis,
Pelargonium graveolens		 C. albicans No data 100–500 Biofilm formation; confocal laser microscopy [35]
2000 1000 Mature biofilm; XTT, crystal violet, and inverted light microscopy [58]
No data 1000–8000 Mature biofilm; XTT [46]
α-Longipinene
(sesquiterpene)		 Croton eluteria,
Helichrysum italicum		 C. albicans No data 100–500 Biofilm formation; confocal laser microscopy [35]
Menthol
(monotherpene)		 Mentha spp. C. albicans >4000 2000 Mature biofilm; XTT, crystal violet, and inverted light microscopy [58]
2500 10,000–80,000 Mature biofilm; XTT [66]
Montanolide
(sesquiterpene lactone)		 Laserpitium ochridanum,
L. zernyi		 C. albicans 200 400 Mature biofilm; luminescence [42]
C. krusei 200 400
Morin
(flavonoid)		 Prunus dulcis ,
Morus alba		 C. albicans 150 37.5–600 Biofilm formation; crystal violet [69]
Myrcene
(monotherpene)		 Humulus lupulus,
Cannabis sativa		 C. albicans 1000 2000 Mature biofilm; XTT, crystal violet, and inverted light microscopy [58]
Nerol
(monotherpene)		 Citrus × aurantium,
Humulus lupulus		 C. albicans 2000 500 Mature biofilm; XTT, crystal violet, and inverted light microscopy [58]
Nerolidols
(sesquiterpene)		 Citrus × aurantium,
Piper claussenianum		 C. albicans 18,600–62,500 2500–10,000 Mature biofilm; MTT [47]
α-Pinene
(monotherpene)		 Pinus sylvestris,
Picea abies		 C. albicans 3125 3125 Biofilm formation; XTT [70]
β-Pinene
(monotherpene)		 Pinus sylvestris,
Picea abies		 C. albicans 2000 4000 Mature biofilm; XTT, crystal violet, and inverted light microscopy [58]
187 187 Biofilm formation; XTT [70]
Polygodial
(sesquiterpene)		 Warburgia ugandensis, Polygonum hydropiper C. albicans 4.1 10.8 Biofilm formation and mature biofilm; XTT and confocal laser microscopy [51]
C. glabrata 94.1 50.6–61.9
Pterostilbene
(polyphenol)		 Pterocarpus marsupium, Pterocarpus santalinus,
Vitis vinifera		 C. albicans No data 8–32 Biofilm formation and mature biofilm; XTT [71]
Riccardin D
(macrocyclic bisbibenzyl)		 Dumortiera hirsuta C. albicans 16 8–64 Mature biofilm; XTT [72]
Salicylaldehyde
(phenolic aldehyde)		 Filipendula ulmaria,
Fagopyrum esculentum		 C. albicans 31 125 Mature biofilm; XTT, crystal violet, and inverted light microscopy [56]
Salicylic acid
(phenolic acid)		 Salix sp.,
Filipendula ulmaria		 C. albicans 4000 2000 Mature biofilm; XTT, crystal violet, and inverted light microscopy [56]
Scopoletin
(cumarin)		 Mitracarpus frigidus,
Scopolia carniola		 C. tropicalis 50 50 Biofilm adhesion, formation, and mature biofilm; absorbance and digital scanning [73]
6-Shogaol
(phenylalkane)		 Zingiber officinale C. auris 32–64 16–64 Mature biofilm; crystal violet [74]
Tarolide
(sesquiterpene lactone)		 Laserpitium ochridanum,
L. zernyi		 C. albicans 400 1000 Mature biofilm; luminescence [42]
C. krusei 400 1000
Telekin
(sesquiterpene lactone)		 Carpesium macrocephalum,
Telekia speciose		 C. albicans >128 36 Biofilm formation and mature biofilm; XTT [65]
Terpinolene
(terpene)		 Cannabis sativa,
Citrus limon		 C. albicans 2000 4000 Mature biofilm; XTT, crystal violet, and inverted light microscopy [58]
5,7,3′,4′-Tetramethoxyflavone
(flavonoid)		 Psiadia punctulate,
Kaempferia parviflora		 C. albicans 100 40 Biofilm formation; crystal violet [75]
α-Thujone
(monotherpene)		 Artemisia absinthium,
Tanacetum vulgare		 C. albicans >4000 500 Mature biofilm; XTT, crystal violet, and inverted light microscopy [58]
Thymol
(phenol)		 Thymus vulgaris,
Trachyspermum copticum		 C. albicans 250 250 Mature biofilm; XTT, crystal violet, and inverted light microscopy [58]
1.56–50 3.12 Biofilm formation; absorbance, crystal violet, and scanning electron microscopy [25]
32–128 128 Biofilm adhesion and mature biofilm; XTT [76]
100–20,000 300–1250 Mature biofilm; XTT [61]
125 125–250 Biofilm formation and mature biofilm; XTT [77]
1200 5000–80,000 Mature biofilm; XTT [66]
C. tropicalis 1.56–50 12.5 Biofilm formation; absorbance, crystal violet, and scanning electron microscopy [25]
C. glabrata 100–20,000 300–1250 Mature biofilm; XTT [61]
C. parapsilosis 100–20,000 300–1250
Tn-AFP1
(protein)		 Trapa natans C. tropicalis 32 16 Mature biofilm; XTT [78]
5,6,8-Trihydroxy-7,4′
dimethoxy flavone
(flavonoid)		 Thymus membranaceus subsp. membranaceus,
Dodonaea viscosa var. angustifolia		 C. albicans 390 390 Biofilm formation and mature biofilm; MTT [79]
5(R)-Vanessine
(alkaloid)		 Waltheria indica C. albicans 32 16 Mature biofilm; XTT [55]
C. glabrata >32 16
C. krusei 32 16
C. parapsilosis >32 16
C. tropicalis >32 16
Vanillic acid
(phenolic acid)		 Angelica sinensis ,
Solanum tuberosum		 C. albicans >4000 4000 Mature biofilm; XTT, crystal violet, and inverted light microscopy [56]
Vanillin
(phenol)		 Vanilla planifolia C. albicans 1000 500 Mature biofilm; XTT, crystal violet, and inverted light microscopy [56]
Waltheriones
(alkaloid)		 Waltheria indica,
W.viscosissima		 C. albicans 4–32 8–32 Mature biofilm; XTT [55]
C. glabrata 32 or >32 8–32
C. krusei 16–32 or >32 8–32
C. parapsilosis 2–32 or >32 8–32
C. tropicalis 32 or >32 8–32
Warburganal
(sesquiterpene)		 Warburgia sp. C. albicans 4 4.5 Biofilm formation and mature biofilm; XTT and confocal laser microscopy [51]
C. glabrata 72–72.6 49.1–55.9
Legend: MIC—minimal inhibitory concentration; XTT—reduction assay of 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[carbonyl(phenylamino)]-2H-tetrazolium hydroxide; MTT—reduction assay of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide [53][54].
In terms of activity, large differences were found, depending on the authors cited. Eugenol and thymol serve as good examples. Both compounds exhibited excellent activity in some studies (from 12.5 mg/L for eugenol [63] and 1.56 mg/L for thymol [25]), and in other studies, the activity was very poor (up to 80,000 for both [66]). These differences may be related, for example, to a different purity of the compound, a different fungal suspension density, or even to the use of other Candida strains with different sensitivities to chemical substances. A number of other factors, such as the type of culture medium, pH of the medium, incubation time, and temperature may likewise influence the antimicrobial activity [80].
According to the European Committee on Antimicrobial Susceptibility Testing (EUCAST), the antifungal clinical breakpoints are between 0.001 mg/L and 16 mg/L [81]. Using EUCAST guidelines in this review, the most active compounds that inhibit (>50%) Candida biofilm formation are lichochalcone A (from 0.2 mg/L) [68], thymol (from 3.12 mg/L) [25], dioscin (from 3.9 mg/L) [30], baicalein (from 4 mg/L) [57], warburganal (4.5 mg/L) [51], pterostilbene, waltheriones and riccardin D (both from 8 mg/L) [55][72][71], polygodial (10.8 mg/L) [51], cannabidiol and eugenol (both from 12.5 mg/L) [63][60], and ivalin (15.4 mg/L) [65]. It is interesting that monotherpenes, which represent the highest percentage of substances listed in Table 2, are not the most active compounds. The two larger groups with the best activity are phenolic compounds (thymol, pterostilbene, and eugenol), and sesquiterpene derivatives (warburganal, polygodial, and ivalin). Single compounds with the highest observed activity belong to chalconoids (lichochalcone A), steroidal saponins (dioscin), flavonoids (baicalein), alkaloids (waltheriones), macrocyclic bisbibenzyls (riccardin D), and cannabinoids (cannabidiol). Most of the compounds presented in Table 2 acted on biofilm formation and/or mature biofilm.

This entry is adapted from the peer-reviewed paper 10.3390/jof7050360

References

  1. Brown, G.D.; Denning, D.W.; Gow, N.A.R.; Levitz, S.M.; Netea, M.G.; White, T.C. Hidden Killers: Human Fungal Infections. Sci. Transl. Med. 2012, 4, 165rv13.
  2. Ciurea, C.N.; Kosovski, I.-B.; Mare, A.D.; Toma, F.; Pintea-Simon, I.A.; Man, A. Candida and Candidiasis-Opportunism Versus Pathogenicity: A Review of the Virulence Traits. Microorganisms 2020, 8, 857.
  3. Moran, G.; Coleman, D.; Sullivan, D. An Introduction to the Medically Important Candida Species. In Candida and Candidiasis, 2nd ed.; Wiley: Hoboken, NJ, USA, 2012; pp. 11–25.
  4. Buranarom, N.; Komin, O.; Matangkasombut, O. Hyposalivation, Oral Health, and Candida Colonization in Independent Dentate Elders. PLoS ONE 2020, 15, e0242832.
  5. Arya, N.R.; Naureen, R.B. Candidiasis. In StatPearls; StatPearls Publishing: Treasure Island, FL, USA, 2021.
  6. Millet, N.; Solis, N.V.; Swidergall, M. Mucosal IgA Prevents Commensal Candida Albicans Dysbiosis in the Oral Cavity. Front. Immunol. 2020, 11, 555363.
  7. Sobel, J.D. Vulvovaginal Candidosis. Lancet 2007, 369, 1961–1971.
  8. Vila, T.; Sultan, A.S.; Montelongo-Jauregui, D.; Jabra-Rizk, M.A. Oral Candidiasis: A Disease of Opportunity. J. Fungi 2020, 6, 15.
  9. Karpiński, T.; Sopata, M.; Mańkowski, B. The Antimicrobial Effectiveness of Antiseptics as a Challenge in Hard to Heal Wounds. Leczenie Ran 2020, 17, 88–94.
  10. Bhattacharya, S.; Sae-Tia, S.; Fries, B.C. Candidiasis and Mechanisms of Antifungal Resistance. Antibiotics 2020, 9, 312.
  11. Cornely, O.A.; Bassetti, M.; Calandra, T.; Garbino, J.; Kullberg, B.J.; Lortholary, O.; Meersseman, W.; Akova, M.; Arendrup, M.C.; Arikan-Akdagli, S.; et al. ESCMID* Guideline for the Diagnosis and Management of Candida Diseases 2012: Non-Neutropenic Adult Patients. Clin. Microbiol. Infect. 2012, 18 (Suppl. 7), 19–37.
  12. Pappas, P.G.; Kauffman, C.A.; Andes, D.R.; Clancy, C.J.; Marr, K.A.; Ostrosky-Zeichner, L.; Reboli, A.C.; Schuster, M.G.; Vazquez, J.A.; Walsh, T.J.; et al. Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America. Clin. Infect. Dis. 2016, 62, e1–e50.
  13. Marak, M.B.; Dhanashree, B. Antifungal Susceptibility and Biofilm Production of Candida Spp. Isolated from Clinical Samples. Int. J. Microbiol. 2018, 2018, 7495218.
  14. Rudramurthy, S.M.; Chakrabarti, A.; Paul, R.A.; Sood, P.; Kaur, H.; Capoor, M.R.; Kindo, A.J.; Marak, R.S.K.; Arora, A.; Sardana, R.; et al. Candida auris Candidaemia in Indian ICUs: Analysis of Risk Factors. J. Antimicrob. Chemother. 2017, 72, 1794–1801.
  15. Mayer, F.L.; Wilson, D.; Hube, B. Candida Albicans Pathogenicity Mechanisms. Virulence 2013, 4, 119–128.
  16. Łaska, G.; Sienkiewicz, A. Antifungal Activity of the Rhizome Extracts of Pulsatilla Vulgaris against Candida Glabrata. Eur. J. Biol. Res. 2019, 9, 93–103.
  17. Gebreyohannes, G.; Nyerere, A.; Bii, C.; Sbhatu, D.B. Challenges of Intervention, Treatment, and Antibiotic Resistance of Biofilm-Forming Microorganisms. Heliyon 2019, 5, e02192.
  18. Pereira, R.; Dos Santos Fontenelle, R.O.; de Brito, E.H.S.; de Morais, S.M. Biofilm of Candida Albicans: Formation, Regulation and Resistance. J. Appl. Microbiol. 2020.
  19. Tumbarello, M.; Fiori, B.; Trecarichi, E.M.; Posteraro, P.; Losito, A.R.; De Luca, A.; Sanguinetti, M.; Fadda, G.; Cauda, R.; Posteraro, B. Risk Factors and Outcomes of Candidemia Caused by Biofilm-Forming Isolates in a Tertiary Care Hospital. PLoS ONE 2012, 7, e33705.
  20. Müller-Sepúlveda, A.; Chevecich, C.C.; Jara, J.A.; Belmar, C.; Sandoval, P.; Meyer, R.S.; Quijada, R.; Moura, S.; López-Muñoz, R.; Díaz-Dosque, M.; et al. Chemical Characterization of Lavandula Dentata Essential Oil Cultivated in Chile and Its Antibiofilm Effect against Candida Albicans. Planta Med. 2020, 86, 1225–1234.
  21. Motamedi, M.; Saharkhiz, M.J.; Pakshir, K.; Amini Akbarabadi, S.; Alikhani Khordshami, M.; Asadian, F.; Zareshahrabadi, Z.; Zomorodian, K. Chemical Compositions and Antifungal Activities of Satureja Macrosiphon against Candida and Aspergillus Species. Curr. Med. Mycol. 2019, 5, 20–25.
  22. Abu-Darwish, M.S.; Cabral, C.; Gonçalves, M.J.; Cavaleiro, C.; Cruz, M.T.; Paoli, M.; Tomi, F.; Efferth, T.; Salgueiro, L. Ziziphora Tenuior, L. Essential Oil from Dana Biosphere Reserve (Southern Jordan); Chemical Characterization and Assessment of Biological Activities. J. Ethnopharmacol. 2016, 194, 963–970.
  23. Abu-Darwish, M.S.; Cabral, C.; Gonçalves, M.J.; Cavaleiro, C.; Cruz, M.T.; Zulfiqar, A.; Khan, I.A.; Efferth, T.; Salgueiro, L. Chemical Composition and Biological Activities of Artemisia Judaica Essential Oil from Southern Desert of Jordan. J. Ethnopharmacol. 2016, 191, 161–168.
  24. Soliman, S.S.M.; Semreen, M.H.; El-Keblawy, A.A.; Abdullah, A.; Uppuluri, P.; Ibrahim, A.S. Assessment of Herbal Drugs for Promising Anti-Candida Activity. BMC Complement. Altern. Med. 2017, 17, 257.
  25. Jafri, H.; Ahmad, I. Thymus Vulgaris Essential Oil and Thymol Inhibit Biofilms and Interact Synergistically with Antifungal Drugs against Drug Resistant Strains of Candida Albicans and Candida Tropicalis. J. Mycol. Med. 2020, 30, 100911.
  26. Wang, Z.-J.; Zhu, Y.-Y.; Yi, X.; Zhou, Z.-S.; He, Y.-J.; Zhou, Y.; Qi, Z.-H.; Jin, D.-N.; Zhao, L.-X.; Luo, X.-D. Bioguided Isolation, Identification and Activity Evaluation of Antifungal Compounds from Acorus Tatarinowii Schott. J. Ethnopharmacol. 2020, 261, 113119.
  27. Said, M.M.; Watson, C.; Grando, D. Garlic Alters the Expression of Putative Virulence Factor Genes SIR2 and ECE1 in Vulvovaginal C. Albicans Isolates. Sci. Rep. 2020, 10, 3615.
  28. Bersan, S.M.F.; Galvão, L.C.C.; Goes, V.F.F.; Sartoratto, A.; Figueira, G.M.; Rehder, V.L.G.; Alencar, S.M.; Duarte, R.M.T.; Rosalen, P.L.; Duarte, M.C.T. Action of Essential Oils from Brazilian Native and Exotic Medicinal Species on Oral Biofilms. BMC Complement. Altern. Med. 2014, 14, 451.
  29. Teodoro, G.R.; Gontijo, A.V.L.; Salvador, M.J.; Tanaka, M.H.; Brighenti, F.L.; Delbem, A.C.B.; Delbem, Á.C.B.; Koga-Ito, C.Y. Effects of Acetone Fraction From Buchenavia Tomentosa Aqueous Extract and Gallic Acid on Candida Albicans Biofilms and Virulence Factors. Front. Microbiol. 2018, 9, 647.
  30. Barros Cota, B.; Batista Carneiro de Oliveira, D.; Carla Borges, T.; Cristina Catto, A.; Valverde Serafim, C.; Rogelis Aquiles Rodrigues, A.; Kohlhoff, M.; Leomar Zani, C.; Assunção Andrade, A. Antifungal Activity of Extracts and Purified Saponins from the Rhizomes of Chamaecostus Cuspidatus against Candida and Trichophyton Species. J. Appl. Microbiol. 2021, 130, 61–75.
  31. Wijesinghe, G.K.; Maia, F.C.; de Oliveira, T.R.; de Feiria, S.N.B.; Joia, F.; Barbosa, J.P.; Boni, G.C.; de Cássia Orlandi Sardi, J.; Rosalen, P.L.; Höfling, J.F. Effect of Cinnamomum Verum Leaf Essential Oil on Virulence Factors of Candida Species and Determination of the In-Vivo Toxicity with Galleria Mellonella Model. Mem. Inst. Oswaldo. Cruz. 2020, 115, e200349.
  32. Pedroso, R.D.S.; Balbino, B.L.; Andrade, G.; Dias, M.C.P.S.; Alvarenga, T.A.; Pedroso, R.C.N.; Pimenta, L.P.; Lucarini, R.; Pauletti, P.M.; Januário, A.H.; et al. In Vitro and In Vivo Anti-Candida Spp. Activity of Plant-Derived Products. Plants 2019, 8, 494.
  33. Andrade, G.; Orlando, H.C.S.; Scorzoni, L.; Pedroso, R.S.; Abrão, F.; Carvalho, M.T.M.; Veneziani, R.C.S.; Ambrósio, S.R.; Bastos, J.K.; Mendes-Giannini, M.J.S.; et al. Brazilian Copaifera Species: Antifungal Activity against Clinically Relevant Candida Species, Cellular Target, and In Vivo Toxicity. J. Fungi 2020, 6, 153.
  34. de Almeida Freires, I.; Murata, R.M.; Furletti, V.F.; Sartoratto, A.; de Alencar, S.M.; Figueira, G.M.; de Oliveira Rodrigues, J.A.; Duarte, M.C.T.; Rosalen, P.L. Coriandrum Sativum L. (Coriander) Essential Oil: Antifungal Activity and Mode of Action on Candida spp., and Molecular Targets Affected in Human Whole-Genome Expression. PLoS ONE 2014, 9, e99086.
  35. Manoharan, R.K.; Lee, J.-H.; Kim, Y.-G.; Kim, S.-I.; Lee, J. Inhibitory Effects of the Essential Oils α-Longipinene and Linalool on Biofilm Formation and Hyphal Growth of Candida Albicans. Biofouling 2017, 33, 143–155.
  36. Khan, M.S.A.; Ahmad, I. Biofilm Inhibition by Cymbopogon Citratus and Syzygium Aromaticum Essential Oils in the Strains of Candida Albicans. J. Ethnopharmacol. 2012, 140, 416–423.
  37. Agarwal, V.; Lal, P.; Pruthi, V. Prevention of Candida Albicans Biofilm by Plant Oils. Mycopathologia 2008, 165, 13–19.
  38. De Toledo, L.G.; Ramos, M.A.D.S.; Spósito, L.; Castilho, E.M.; Pavan, F.R.; Lopes, É.D.O.; Zocolo, G.J.; Silva, F.A.N.; Soares, T.H.; Dos Santos, A.G.; et al. Essential Oil of Cymbopogon Nardus (L.) Rendle: A Strategy to Combat Fungal Infections Caused by Candida Species. Int. J. Mol. Sci. 2016, 17, 1252.
  39. Hendry, E.R.; Worthington, T.; Conway, B.R.; Lambert, P.A. Antimicrobial Efficacy of Eucalyptus Oil and 1,8-Cineole Alone and in Combination with Chlorhexidine Digluconate against Microorganisms Grown in Planktonic and Biofilm Cultures. J. Antimicrob. Chemother. 2009, 64, 1219–1225.
  40. Quatrin, P.M.; Verdi, C.M.; de Souza, M.E.; de Godoi, S.N.; Klein, B.; Gundel, A.; Wagner, R.; de Almeida Vaucher, R.; Ourique, A.F.; Santos, R.C.V. Antimicrobial and Antibiofilm Activities of Nanoemulsions Containing Eucalyptus Globulus Oil against Pseudomonas Aeruginosa and Candida spp. Microb. Pathog. 2017, 112, 230–242.
  41. Sardi, J.d.C.O.; Freires, I.A.; Lazarini, J.G.; Infante, J.; de Alencar, S.M.; Rosalen, P.L. Unexplored Endemic Fruit Species from Brazil: Antibiofilm Properties, Insights into Mode of Action, and Systemic Toxicity of Four Eugenia spp. Microb. Pathog. 2017, 105, 280–287.
  42. Popović, V.; Stojković, D.; Nikolić, M.; Heyerick, A.; Petrović, S.; Soković, M.; Niketić, M. Extracts of Three Laserpitium L. Species and Their Principal Components Laserpitine and Sesquiterpene Lactones Inhibit Microbial Growth and Biofilm Formation by Oral Candida Isolates. Food. Funct. 2015, 6, 1205–1211.
  43. Benzaid, C.; Belmadani, A.; Djeribi, R.; Rouabhia, M. The Effects of Mentha × Piperita Essential Oil on C. Albicans Growth, Transition, Biofilm Formation, and the Expression of Secreted Aspartyl Proteinases Genes. Antibiotics 2019, 8, 10.
  44. Cannas, S.; Molicotti, P.; Usai, D.; Maxia, A.; Zanetti, S. Antifungal, Anti-Biofilm and Adhesion Activity of the Essential Oil of Myrtus Communis L. against Candida Species. Nat. Prod. Res. 2014, 28, 2173–2177.
  45. Stojković, D.; Dias, M.I.; Drakulić, D.; Barros, L.; Stevanović, M.; C F R Ferreira, I.; D Soković, M. Methanolic Extract of the Herb Ononis Spinosa L. Is an Antifungal Agent with No Cytotoxicity to Primary Human Cells. Pharmaceuticals 2020, 13, 78.
  46. Souza, C.M.C.; Pereira Junior, S.A.; Moraes, T.d.S.; Damasceno, J.L.; Amorim Mendes, S.; Dias, H.J.; Stefani, R.; Tavares, D.C.; Martins, C.H.G.; Crotti, A.E.M.; et al. Antifungal Activity of Plant-Derived Essential Oils on Candida Tropicalis Planktonic and Biofilms Cells. Med. Mycol. 2016, 54, 515–523.
  47. Curvelo, J.A.R.; Marques, A.M.; Barreto, A.L.S.; Romanos, M.T.V.; Portela, M.B.; Kaplan, M.A.C.; Soares, R.M.A. A Novel Nerolidol-Rich Essential Oil from Piper Claussenianum Modulates Candida Albicans Biofilm. J. Med. Microbiol. 2014, 63, 697–702.
  48. Bakkiyaraj, D.; Nandhini, J.R.; Malathy, B.; Pandian, S.K. The Anti-Biofilm Potential of Pomegranate (Punica Granatum L.) Extract against Human Bacterial and Fungal Pathogens. Biofouling 2013, 29, 929–937.
  49. Alves-Silva, J.M.; Zuzarte, M.; Gonçalves, M.J.; Cruz, M.T.; Cavaleiro, C.; Salgueiro, L. Unveiling the Bioactive Potential of the Essential Oil of a Portuguese Endemism, Santolina Impressa. J. Ethnopharmacol. 2019, 244, 112120.
  50. Sharifzadeh, A.; Khosravi, A.R.; Ahmadian, S. Chemical Composition and Antifungal Activity of Satureja Hortensis L. Essentiall Oil against Planktonic and Biofilm Growth of Candida Albicans Isolates from Buccal Lesions of HIV(+) Individuals. Microb. Pathog. 2016, 96, 1–9.
  51. Kipanga, P.N.; Liu, M.; Panda, S.K.; Mai, A.H.; Veryser, C.; Van Puyvelde, L.; De Borggraeve, W.M.; Van Dijck, P.; Matasyoh, J.; Luyten, W. Biofilm Inhibiting Properties of Compounds from the Leaves of Warburgia Ugandensis Sprague Subsp. Ugandensis against Candida and Staphylococcal Biofilms. J. Ethnopharmacol. 2020, 248, 112352.
  52. Gabriela, N.; Rosa, A.M.; Catiana, Z.I.; Soledad, C.; Mabel, O.R.; Esteban, S.J.; Veronica, B.; Daniel, W.; Ines, I.M. The Effect of Zuccagnia Punctata, an Argentine Medicinal Plant, on Virulence Factors from Candida Species. Nat. Prod. Commun. 2014, 9, 933–936.
  53. Karpiński, T.M. Efficacy of Octenidine against Pseudomonas Aeruginosa Strains. Eur. J. Biol. Res. 2019, 9, 135–140.
  54. Loures, F.V.; Levitz, S.M. XTT Assay of Antifungal Activity. Bio. Protoc. 2015, 5, e1543.
  55. Cretton, S.; Dorsaz, S.; Azzollini, A.; Favre-Godal, Q.; Marcourt, L.; Ebrahimi, S.N.; Voinesco, F.; Michellod, E.; Sanglard, D.; Gindro, K.; et al. Antifungal Quinoline Alkaloids from Waltheria Indica. J. Nat. Prod. 2016, 79, 300–307.
  56. Raut, J.S.; Shinde, R.B.; Chauhan, N.M.; Karuppayil, S.M. Phenylpropanoids of Plant Origin as Inhibitors of Biofilm Formation by Candida Albicans. J. Microbiol. Biotechnol. 2014, 24, 1216–1225.
  57. Cao, Y.; Dai, B.; Wang, Y.; Huang, S.; Xu, Y.; Cao, Y.; Gao, P.; Zhu, Z.; Jiang, Y. In Vitro Activity of Baicalein against Candida Albicans Biofilms. Int. J. Antimicrob. Agents 2008, 32, 73–77.
  58. Raut, J.S.; Shinde, R.B.; Chauhan, N.M.; Karuppayil, S.M. Terpenoids of Plant Origin Inhibit Morphogenesis, Adhesion, and Biofilm Formation by Candida Albicans. Biofouling 2013, 29, 87–96.
  59. Ivanov, M.; Kannan, A.; Stojković, D.S.; Glamočlija, J.; Calhelha, R.C.; Ferreira, I.C.F.R.; Sanglard, D.; Soković, M. Camphor and Eucalyptol-Anticandidal Spectrum, Antivirulence Effect, Efflux Pumps Interference and Cytotoxicity. Int. J. Mol. Sci. 2021, 22, 483.
  60. Feldman, M.; Sionov, R.V.; Mechoulam, R.; Steinberg, D. Anti-Biofilm Activity of Cannabidiol against Candida Albicans. Microorganisms 2021, 9, 441.
  61. Dalleau, S.; Cateau, E.; Bergès, T.; Berjeaud, J.-M.; Imbert, C. In Vitro Activity of Terpenes against Candida Biofilms. Int. J. Antimicrob. Agents 2008, 31, 572–576.
  62. Touil, H.F.Z.; Boucherit, K.; Boucherit-Otmani, Z.; Khoder, G.; Madkour, M.; Soliman, S.S.M. Optimum Inhibition of Amphotericin-B-Resistant Candida Albicans Strain in Single- and Mixed-Species Biofilms by Candida and Non-Candida Terpenoids. Biomolecules 2020, 10, 342.
  63. Khan, M.S.A.; Ahmad, I. Antibiofilm Activity of Certain Phytocompounds and Their Synergy with Fluconazole against Candida Albicans Biofilms. J. Antimicrob. Chemother. 2012, 67, 618–621.
  64. Janeczko, M.; Masłyk, M.; Kubiński, K.; Golczyk, H. Emodin, a Natural Inhibitor of Protein Kinase CK2, Suppresses Growth, Hyphal Development, and Biofilm Formation of Candida Albicans. Yeast 2017, 34, 253–265.
  65. Xie, C.; Sun, L.; Meng, L.; Wang, M.; Xu, J.; Bartlam, M.; Guo, Y. Sesquiterpenes from Carpesium Macrocephalum Inhibit Candida Albicans Biofilm Formation and Dimorphism. Bioorg. Med. Chem. Lett. 2015, 25, 5409–5411.
  66. Pemmaraju, S.C.; Pruthi, P.A.; Prasad, R.; Pruthi, V. Candida Albicans Biofilm Inhibition by Synergistic Action of Terpenes and Fluconazole. Indian J. Exp. Biol. 2013, 51, 1032–1037.
  67. Ali, I.; Khan, F.G.; Suri, K.A.; Gupta, B.D.; Satti, N.K.; Dutt, P.; Afrin, F.; Qazi, G.N.; Khan, I.A. In Vitro Antifungal Activity of Hydroxychavicol Isolated from Piper Betle L. Ann. Clin. Microbiol. Antimicrob. 2010, 9, 7.
  68. Messier, C.; Grenier, D. Effect of Licorice Compounds Licochalcone A, Glabridin and Glycyrrhizic Acid on Growth and Virulence Properties of Candida Albicans. Mycoses 2011, 54, e801–e806.
  69. Abirami, G.; Alexpandi, R.; Durgadevi, R.; Kannappan, A.; Veera Ravi, A. Inhibitory Effect of Morin Against Candida Albicans Pathogenicity and Virulence Factor Production: An in Vitro and in Vivo Approaches. Front. Microbiol. 2020, 11, 561298.
  70. Rivas da Silva, A.C.; Lopes, P.M.; Barros de Azevedo, M.M.; Costa, D.C.M.; Alviano, C.S.; Alviano, D.S. Biological Activities of α-Pinene and β-Pinene Enantiomers. Molecules 2012, 17, 6305–6316.
  71. Hu, D.-D.; Zhang, R.-L.; Zou, Y.; Zhong, H.; Zhang, E.-S.; Luo, X.; Wang, Y.; Jiang, Y.-Y. The Structure-Activity Relationship of Pterostilbene Against Candida Albicans Biofilms. Molecules 2017, 22, 360.
  72. Cheng, A.; Sun, L.; Wu, X.; Lou, H. The Inhibitory Effect of a Macrocyclic Bisbibenzyl Riccardin D on the Biofilms of Candida Albicans. Biol. Pharm. Bull. 2009, 32, 1417–1421.
  73. Lemos, A.S.O.; Florêncio, J.R.; Pinto, N.C.C.; Campos, L.M.; Silva, T.P.; Grazul, R.M.; Pinto, P.F.; Tavares, G.D.; Scio, E.; Apolônio, A.C.M.; et al. Antifungal Activity of the Natural Coumarin Scopoletin Against Planktonic Cells and Biofilms From a Multidrug-Resistant Candida Tropicalis Strain. Front. Microbiol. 2020, 11, 1525.
  74. Kim, H.-R.; Eom, Y.-B. Antifungal and Anti-Biofilm Effects of 6-Shogaol against Candida Auris. J. Appl. Microbiol. 2020.
  75. Dal Piaz, F.; Bader, A.; Malafronte, N.; D’Ambola, M.; Petrone, A.M.; Porta, A.; Ben Hadda, T.; De Tommasi, N.; Bisio, A.; Severino, L. Phytochemistry of Compounds Isolated from the Leaf-Surface Extract of Psiadia Punctulata (DC.) Vatke Growing in Saudi Arabia. Phytochemistry 2018, 155, 191–202.
  76. Shu, C.; Sun, L.; Zhang, W. Thymol Has Antifungal Activity against Candida Albicans during Infection and Maintains the Innate Immune Response Required for Function of the P38 MAPK Signaling Pathway in Caenorhabditis Elegans. Immunol. Res. 2016, 64, 1013–1024.
  77. Braga, P.C.; Culici, M.; Alfieri, M.; Dal Sasso, M. Thymol Inhibits Candida Albicans Biofilm Formation and Mature Biofilm. Int. J. Antimicrob. Agents 2008, 31, 472–477.
  78. Mandal, S.M.; Migliolo, L.; Franco, O.L.; Ghosh, A.K. Identification of an Antifungal Peptide from Trapa Natans Fruits with Inhibitory Effects on Candida Tropicalis Biofilm Formation. Peptides 2011, 32, 1741–1747.
  79. Patel, M.; Srivastava, V.; Ahmad, A. Dodonaea Viscosa Var Angustifolia Derived 5,6,8-Trihydroxy-7,4’ Dimethoxy Flavone Inhibits Ergosterol Synthesis and the Production of Hyphae and Biofilm in Candida Albicans. J. Ethnopharmacol. 2020, 259, 112965.
  80. Karpiński, T.M. Essential Oils of Lamiaceae Family Plants as Antifungals. Biomolecules 2020, 10, 103.
  81. EUCAST: Breakpoints for Antifungals. Available online: (accessed on 19 March 2021).
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