## 4 Discussion  
### The Antifungal Activity of LIN  
The incidence of fungal infections, especially those caused by _Candida_ spp., has recently been steadily increasing, mainly in immunocompromised persons. Their treatment is often inefficient due to the growing resistance of fungi to standard antifungals. This fact is a challenge for clinicians and researchers dealing with the treatment of candidiasis [43] and emphasizes the need to search for new alternative therapies, e.g., from natural sources in combination with other strategies [7; 10]. Therefore, we decided to verify the antifungal potential of LIN against 16 reference fungal strains from four species: _Candida_ spp., _Cryptococcus_ spp., _Geotrichum_ spp., and _Saccharomyces_ spp., which varied in the range of MIC = MFC = 0.5-8 mg/mL. The ratios of MFC/MIC = 1-4 suggested a beneficial fungicidal effect of terpene on these yeasts. In the case of _Candida_ spp., LIN showed activity at MIC = 1-8 mg/mL and MFC = 2-8 mg/mL. The susceptibility of 40 oral isolates from patients with hematological malignancies was similar (MIC = 0.5-8 mg/mL, and MFC = 1-16 mg/mL). Most of the tested _Candida_ isolates were inhibited by LIN at MIC = 2-4 mg/mL and only single strains were susceptible to terpene at MIC = 0.5 mg/mL. On the basis of the MFC/MIC ratios, its fungicidal activity was also confirmed. Similar data were presented by [PERSON] et al. [44]. They analyzed in vitro the antifungal effect of LIN toward isolates of _Candida_ spp. from 12 patients with clinical diagnoses of oral candidiasis caused by the use of dentures. In addition, half of these persons reported having diabetes, and five persons reported having inadequate hygiene of oral cavity. MICs and MFCs of LIN were within the range 0.5-2 mg/mL against _C. albicans_, _C. tropicalis_, and _C. krusei_. LIN exhibited fungicidal effect with MFC/MIC = 1-2. The best activity of this terpene was observed toward _C. tropicalis_ (MIC = MFC = 0.5 mg/mL), followed by _C. albicans_ (MIC = 1-2 mg/mL, MFC = 2 mg/mL) and _C. krusei_ (MIC = MFC = 2 mg/mL). Moreover, MICs and MFCs of nystatin, as in our research, were significantly lower (in the range 0.39-0.78 \(\mathrm{\SIUnitSymbolMicro g}\)/mL). [PERSON] et al. [9] also exhibited interesting results with MIC of LIN ranged from 1 to 2 mg/mL against _C. albicans_ ATCC 90028 strain and clinical _C. albicans_ isolates. In the next studies performed by [PERSON] et al. [16], MIC values of this terpene were 0.79-1.58 mg/mL toward two clinical isolates of _C. albicans_. Anticandidal activity of LIN was also tested by [PERSON] et al. [45] and results were similar to that of ours, with MIC = 0.9 mg/mL and MFC = 2.6 mg/mL against both reference and clinical _C. albicans_ strains. Moreover, other data indicated activity of LIN toward _C. albicans_ with MIC of 1.6 mg/mL [46] or MIC = 0.75 mg/mL [47]. In turn, a slightly higher activity of this terpene was found by further authors. The results obtained by [PERSON] et al. [26] showed that 12 strains of _C. albicans_ (of which 64.28% included fluconazole-resistant isolates) were sensitive to LIN at MIC = 64-128 \(\mathrm{\SIUnitSymbolMicro g}\)/mL and MFC = 128-256 \(\mathrm{\SIUnitSymbolMicro g}\)/mL with MFC/MIC = 1-4 and fungicidal effect. The susceptibility to LIN of reference strains _C. albicans_ ATCC 76485 and _C. albicans_ SC 5314 ATCC MYA-2876 was similar (MIC = 64 ug/mL, and MFC = 128 ug/mL). In turn, the activity of nystatin was in the ranges MIC = 4-8 ug/mL and MFC = 4-32 ug/mL. In accordance with other studies [28], clinical _C. Krusei_ isolates were inhibited by LIN at MICs between 100-200 ug/mL. Its MFC values were 1-2 times greater than the respective MIC values, suggesting that studied terpene showed fungicidal activity. Further data [48] exhibited that LIN inhibited the growth of _C. tropicalis_ ATCC 13803 at a concentration of 125 ug/mL. Subsequent results for LIN by [PERSON] et al. [49] varied significantly; its mean of MIC value against _C. albicans_ isolated from human cutaneous candidiasis was 13.52 ug/mL.