|
|
Antifungal resistance mechanisms in dermatophytes
Kolarczyková, Daniela ; Hubka, Vít (advisor) ; Kuklová, Ivana (referee)
For the treatment of superficial fungal infections (dermatophytosis) is available a wide spectrum of antifungals from various chemical groups. These antifungals are mainly focused on various steps of ergosterol synthesis, thereby disrupting the cell membrane (allylamine, azole and morpholine antifungals) and on microtubule function (benzofuran antifungals). Despite the fact that the treatment of dermatophytosis is often associated with long-term exposure of the fungus to antifungals (weeks or months), until recently antifungal resistance in dermatophytes has been considered rare. However, current studies have shown the incidence of chronic infections, reinfection and treatment failures due to emerging resistance to some commonly used antifungals. The most serious problem today is the spread of resistance to terbinafine where the molecular principles are founded in the structural changes in the squalene epoxidase enzyme (SQLE). The increase in the incidence of this and other resistances is currently alarming especially in India, while the situation in Europe and America is in terms of dermatophyte susceptibility still quite favorable. The aim of this thesis is to summarize our knowledge of antifungal resistance in dermatophytes and their molecular principles. The thesis further summarizes the...
|
|
|
Genetic background and spread of azole resistance in Aspergillus fumigatus
Holíková, Kristýna ; Hubka, Vít (advisor) ; Lysková, Pavlína (referee)
Aspergillus is a globally widespread saprophytic filamentous genus of fungi, including opportunistic pathogenic species that cause a disease called aspergillosis. Azole derivatives have an irreplaceable role in the treatment of aspergillosis. These drugs inhibit the biosynthetic pathway of ergosterol. That leads to disruption of the fungal plasma membrane. However, nowadays, the rate of occurrence of azole-resistant fungi is rapidly increasing, which also increases the mortality of the patients. The aim of this bachelor thesis is to summarize the current knowledge associated with azole resistance with focus on its genetic background and global distribution. The main emphasis is given on the species Aspergillus fumigatus which is the most common agent of aspergillosis. Resistance to azole derivatives arises from prolonged fungi exposure to azole drugs or fungicides. The most common origin of azole resistance relates to the use of azole fungicides in agriculture. There are several ways how the resistance works. Most of them, however, relate to changes in the cyp51A gene, which is affected by azoles, and its promoter, with the most frequent mutation being TR34/L98H. The most common mechanism of the resistance that is not associated with changes in the cyp51A gene is increased expression of efflux...
|
guest ::
