Maltol, 3-hydroxy-2-methyl-4-pyrone (Figure 1A), a naturally occurring compound, can be isolated from various types of plants, such as bark and leaves of Larix deciduas, Evodiopanax innovans, Cercidiphyllum japonicum, Citharexylum spinosum, Passiflora incarnata, Panax ginseng, and different kinds of pine plants [1,2,3,4].
Maltol, mostly used as a flavoring molecule, also has various potential applications as a biomedical compound. Despite its extensive use in the food industry, maltol’s antimicrobial activity was evaluated only briefly, and was suggested to be insufficient on its own. Recently, we have shown that maltol can be used in conjunction with cationic surfactant species to receive higher activity against contaminant microorganisms[1][2][3][4]. In this paper, we have broadened the antimicrobial efficacy studies and evidenced maltol’s mode of action against Gram-negative, Gram-positive bacteria, and fungi. In addition, to increase its efficacy, blends of maltol and two selected cationic surfactants, dodecyl-dimethyl-ammonium chloride (DDAC) and polyquaternium 80 (P-80), were appraised for their activity. Broad efficacy studies revealed synergistic interactions between maltol and both cationic surfactants against most of the tested microorganisms. Electron microscopy images were used to evaluate the microorganisms’ morphology following treatment, pinpointing the specific cell wall damage caused by each of the compounds. Our findings indicate that maltol’s effect on the microbial cell wall can be complemented by catalytic amounts of selected cationic surfactants to enhance and extend its activity. Such a solution can be used as a broad-spectrum preservative for personal care products in cosmetic applications.
Few studies demonstrated that maltol can also be produced by some actinobacteria [5][6][5,6] and a mold species [7]. Maltol is a chelating agent, which binds hard metal centers, such as Fe3+ (Ferric maltol; Figure 1B), Ga3+, Al3+, and VO2+ [8]. Due to its solubility in aqueous solution, maltol was shown to increase the absorption of several essential metals in animal and human subjects, in comparison to hydrophobic chelating molecules[8][9][10][11][12] [9,10,11,12]. Maltol is widely used in the food industry as a flavoring agent, food additive, and a food preservative. Maltol, known for its characteristic sweet smell, is used to create a sweet aroma in fragrances, freshly baked bread, and cakes. In addition to its extensive use in the food industry, maltol was found to have broad applications, such as a biomedical compound [1][13][14][15][16][1,13,14,15,16] and even used as a pest control agent [17]. Maltol is a promising candidate molecule for medical purposes and an important compound in the food industry; moreover, toxicity studies have determined that maltol is non-toxic and generally recognized as safe (GRAS) [7][18][7,18].
The antimicrobial activity of maltol, on the other hand, was only briefly investigated in several previous studies [19][20][4,19,20], while its efficacy was suggested mostly as insufficient on its own [21][22][19,21]. Recent study discovered that maltol efficacy can be significantly increased by the addition of only small amounts of selected cationic surfactants [20]. In this study, the efficacy studies were widened to better understand the mode of action of maltol and its combination with two cationic surfactants, polyquaternium 80 (P-80), and didecyldimethylammonium chloride (DDAC). For this purpose, the antimicrobial mechanism of maltol and its cationic surfactant combinations were evaluated against the five pharmacopeia microorganisms, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans, and Aspergillus brasiliensis, using multiple efficacy studies, morphological examination via electron microscopy imaging, and cell permeability assay.
Separate MIC | 100 | (ppm) | Combined MIC | 100 | (ppm) | Combined MIC | 100 | (ppm) | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Maltol | DDAC | P80 | Maltol | DDAC | Maltol | P80 | |||||||||||||||
E. coli | 4000 | 3.12 | 250 | 250 | 0.78 | 500 | 31.25 | ||||||||||||||
FICI = 0.31 | FICI = 0.25 | ||||||||||||||||||||
S. aureus | 4000 | 0.5 | 7.8 | 62.5 | 0.25 | 250 | 4 | ||||||||||||||
FICI = 0.52 | FICI = 0.58 | ||||||||||||||||||||
P. aeruginosa | 1000 | 12.5 | 1000 | 62.5 | 6.25 | 250 | 62.5 | ||||||||||||||
FICI = 0.56 | FICI = 0.31 | ||||||||||||||||||||
C. albicans | 2000 | 3.12 | 500 | 500 | 0.78 | 125 | 62.5 | ||||||||||||||
FICI = 0.5 | FICI = 0.19 | ||||||||||||||||||||
A. brasiliensis | 4000 | 6.25 | 500 | 500 | 1.56 | 500 | 125 | ||||||||||||||
FICI = 0.38 | FICI = 0.38 |