Candida · Fungal pathogens · Drug resistance · Antifungals · Multi-drug resis-

Candida species are at the top of the list of total infections and cause both super­cial (mucosal and skin infections) and systemic infections (Papon etal. 2013). Common species associated with candidiasis are Candida albicans, Candida parap- silosis, Candida tropicalis, Candida glabrata, Candida krusei, and Candida auris. Next is Aspergillus spp., and depending on the host’s immunological system, it leads to numerous infections in humans. The Aspergillus species that cause infec­tions in humans are Aspergillus fumigatus, Aspergillus avus, Aspergillus terreus, Aspergillus niger, and Aspergillus nidulans. People with compromised lung func­tion, such as those with asthma or cystic brosis, might develop allergic broncho­pulmonary aspergillosis, a hypersensitivity reaction to fungal components. Repeated interaction with conidia can cause non-invasive aspergillomas, which may be due to underlying pulmonary cavities such as healed lesions in patients with tuberculosis (Dagenais and Keller 2009). The encapsulated fungus Cryptococcus neoformans infects both humans and animals. C. neoformans may spread to the blood and enter the central nervous system if the immune system is unable to keep it in the lungs. This might result in deadly meningoencephalitis. (Chen etal. 2022). The fungal infections are treated with three primary antifungal classes, including azoles, poly­enes, and echinocandins (Fairlamb et al. 2016). Azoles target lanosterol 14α-demethylase (encoded by ERG11), which is essential for ergosterol biosynthe­sis, an important component of the fungal cell membrane (Hossain etal. 2022). Azole resistance has already been observed in clinical samples and molecular anal­yses suggest that either mutations in the target enzyme or increased expression of efux pumps that eject the drug from the cell are the main cause. Polyenes, such as amphotericin B (AmpB), bind and sequester ergosterol and form membrane pores

Fig. 7.2 Different resistance mechanisms in fungi to available antifungals. (a) Overexpression of efux transporters in response to exposure to antifungals. (b) Mutation in the target gene ERG11 upon exposure to azoles and echinocandins. (c) Overexpression of HSPs. (d) Alteration of cell wall composition. (e) Mutation in the Fks1/2 proteins in response to echinocandin exposure. Abbreviation: HSPs Heat Shock Proteins