Fungal infections belong to the most often diseases of humans. It is estimated that about 1.7 billion people (25% of the population) have skin, nail, and hair fungal infections [1]. The development of most of these infections is affected by dermatophytes, namely Trichophyton spp., Microsporum spp., and Epidermophyton  spp. [2]. Simultaneously, mucosal infections of the oral and genital tracts caused by Candida  spp. are very common. About 0.13 billion of women suffer from vulvovaginal candidiasis. On the other hand, oral candidiases are common in babies and denture wearers. Fungi also cause life-threatening systemic infections, with mortality reaching >1.6 million, which is >3-fold more than malaria [3]. Among life-threatening fungal infections prevail cryptococcosis (Cryptococcus neoformans) with >1,000,000 cases and mortality rate 20–70%, candidiasis (Candida albicans) with >400,000 cases and mortality rate 46–75%, pneumocystosis (Pneumocystis jirovecii) with >400,000 cases and mortality rate 20–80%, and aspergillosis (Aspergillus fumigatus) with >200,000 cases and mortality rate 30–95% ^[1][4][5][1,4,5]. In  Table 1 are presented diseases caused by some of the most often fungal pathogens among people.

The big problem is growing drug-resistance amid fungi. Among Candida and Aspergillus species is observed resistance to azoles, e.g., to fluconazole, voriconazole, and posaconazole. Some Candida species, especially C. glabrata and C. parapsilosis,  can be echinocandin- and multidrug-resistant ^[8][9][8,9]. Acquired resistance to echinocandins has also been reported for yeasts C. albicans, C. tropicalis, C. krusei, C. kefyr, C. lusitaniae, and C. dubliniensis ^[10] [10]. More than 3% of Aspergillus fumigatus  isolates are resistant to one or more azoles [11]. Polyene resistance mainly concerns amphotericin B. Resistance to this drug is observed in Fusarium spp., Trichosporon spp., Aspergillus spp., and Sporothrix schenckii ^[12][13] [12,13]. Resistance to amphotericin B has also been reported for C. albicans, C. glabrata, and C. tropicalis ^[14][15][16] [14,15,16]. Cultures of some Candida species and Cryptococcus neoformans are presented in Figure 1.

The new epidemiological problem is C. auris, a multidrug-resistant organism first described in Japan in 2009 [17]. Recently, C. auris  has been reported from 36 countries from six continents [18]. About 30% of isolates demonstrate reduced susceptibility to amphotericin B, and 5% can be resistant to the echinocandins ^[19][20][19,20]. The estimated mortality from C. auris  fungemia range from 28% to 60% [21].

Fundamental issues are also the costs of treatment and hospitalization of patients with invasive fungal diseases. According to Drgona et al., all costs range from around €26,000 up to over €80,000 per patient [5].

2. Components of Essential Oils of Lamiaceae Family

The family Lamiaceae or Labiatae contains many valuable medicinal plants. In the family are 236 genera and between 6900 and 7200 species. To the most abundant genera belong Salvia (900 species), Scutellaria (360), Stachys (300), Plectranthus (300), Hyptis (280), Teucrium (250), Vitex (250), Thymus (220), and Nepeta  (200). Lamiaceae plants rich in essential oils have great worth in natural medicine, pharmacology, cosmetology, and aromatherapy ^[22][25]. The essential oils are mostly present in leaves, however, they can be found in flowers, buds, fruits, seeds, rind, wood, or roots ^[23][26]. Essential oils are mixtures of volatile compounds, which are secondary plant metabolites. They play a role in the defense system of higher plants ^[24][27]. Essential oils may contain over 300 different compounds, mainly of molecular weight below 300 ^[25][28]. Some oils, e.g., obtained from Lavandula, Geranium, or Rosmarinus,  contain 450 to 500 chemicals ^[26][29]. Among the active compounds of essential oils are various chemical classes, e.g., alcohols, ethers, aldehydes, ketones, esters, phenols, terpenes (monoterpenes, sesquiterpenes), and coumarins ^[27][28][30,31]. To the chemical components most commonly found as the main ingredients in essential oils, among plants presented in Table 2, include β-caryophyllene (41 plants), linalool (27 plants), limonene (26), β-pinene (25), 1,8-cineole (22), carvacrol (21), α-pinene (21), p-cymene (20), γ-terpinene (20), and thymol (20) (Figure 2). Sesquiterpene β-caryophyllene seems particularly important antifungal component in the Lamiaceae family. Its activity and its derivatives, such as caryophyllene oxide is well known ^[29][30][31][134,135,136]. According to Bona et al. ^[32][137], essential oils containing high concentrations of phenolic monoterpenes (e.g., carvacrol, p-cymene, thymol) have great antifungal activities. Rich in these substances are, among others Origanum and Thymus  plants. Important antifungal chemicals often presented in Lamiaceae are also other monoterpenes as alcohol linalool and cyclic 1,8-cineole, limonene, pinenes, and terpinenes ^{[33][34][35][36][37][38][39][40][41]}[138,139,140,141,142,143,144,145,146]. Table 1 shows that all of these antifungal substances are common in presented plants.

3. Antifungal Activity of Essential Oils of Lamiaceae Family

In Table 3 are shown the antifungal activities of selected Lamiaceae essential oils. More than half of the essential oils have good activity (<1000 µg/mL) against fungi. In some cases are observed significant discrepancies between different studies. An example could be the action of essential oils from Italian Calamintha nepeta against Candida albicans. In the work of Marongiu et al. ^[42][39], minimal inhibitory concentrations amounted to 1.25–2.5 µg/mL, while in Božović et al. ^[43][40] MICs were between 780 to 12,480 µg/mL. Differences may be related to the different biochemical composition of the examined essential oils. In results presented by Marongiu et al. ^[42] [39] the main components of essential oils were pulegone (39.9–64.4%), piperitenone oxide (2.5–19.1%) and piperitenone (6.4–7.7%), while in Božović et al. ^[43][40] three main substances were pulegone (37.7–84.7%), crysanthenone (1.3–33.9%) and menthone (0.5–35.4%). Some authors have described that the content of active substances varies depending on the season. In studies of Gonçalves et al. ^[44] [60] in Mentha cervina  during the flowering phase in August amount of isomenthone and pulegone in essential oil amounted 8.7% and 75.1% respectively. Simultaneously, in the vegetative phase in February, the content of both components changed significantly and amounted to 77.0% for isomenthone and 12.9% for pulegone. Similarly, Al-Maskri et al. ^[45] [75] presented essential changes in some compounds of Ocimum basilicum essential oil between winter and summer. In the summer essential oil, there is significantly more of linalool, p-allylanisole and β-farnesene, and at the same time much less content of limonene and 1,8-cineole. In this work, a seasonal variation of chemical composition is directly related to other antifungal activities. It is particularly evident in action against Aspergillus niger, which was lower in the summer season. Zone of growth inhibition (ZOI) for winter essential oil was 21 mm and MIC > 50 µg/mL, while for summer essential oil-ZOI was 13 mm and MIC > 100 µg/mL ^[45][75]. Influence on the content of chemical substances in essential oils also has a method of obtaining them. Ćavar et al. ^[43] [40] compared the composition of oils obtained from Calamintha glandulosa  using three methods: Hydrodistillation (HD), steam distillation (SD) and aqueous reflux extraction (ARE). For example, the level of menthone was 3.3% in ARE, 4.7% in HD, and 8.3% in SD method, while for shisofuran was only 0.1% in HD and SD, and even 9.7% in ARE ^[43][40]. Additionally, many other factors can affect antimicrobial activity, such as amount and concentration of inoculum, type of culture medium, pH of the medium and incubation time. All these factors can affect the value of MIC ^[40][145]. Differences are visible in Table 2. Generally, it can be assumed that the best activity (MICs < 100) have essential oils from Clinopodium spp. (excluding C. nepeta subsp. glandulosum and C. umbrosum), Lavandula spp., Mentha spp. (excluding M. piperita), Thymbra spp., and Thymus spp. (excluding T. migricus and T. vulgaris). The highest values of MICs are presented among others for Aeollanthus suaveolens, Agastache rugosa, Lepechinia mutica, Mentha × piperita, and Salvia sclarea. Simultaneously, some essential oils have a very different activity, and MIC values differ depending on the region, chemical composition, research methodology, etc. Significant variations can be observed even in Ocimum basilicum (MICs 1–10,000), O. sanctum (MICs 0.1–500), Origanum majorana (MICs 0.5–14,400) or in Thymus vulgaris (MICs 0.08–3600). The mode of action of essential oils is multidirectional. Essential oils lead to disruption of the cell wall and cell membrane through a permeabilization process. The lipophilic compounds of essential oils can pass through the cell wall and damage polysaccharides, fatty acids, and phospholipids, eventually making them permeable ^[41][134][146,147]. Change of the permeability for H⁺ and K⁺  cations affects cellular pH and damage of cellular organelles ^[135][136][148,149]. Additionally, essential oils inhibit the synthesis of fungal DNA, RNA, proteins, and polysaccharides ^[137][150]. Essential oils can also disintegrate mitochondrial membrane ^[138][139][151,152]. It has also been shown that essential oil from Thymus vulgaris inhibits the production of aflatoxins by Aspergillus flavus  and leads to the reduction of ergosterol production ^[127][123].