Antifungal agents: Mode of action, mechanisms of resistance, and correlation of these mechanisms with bacterial resistance

The increased use of antibacterial and antifungal agents in recent years ha s resulted in the development of resistance to these drugs. The significant clinical implication of resistance has led to heightened interest in the s tudy of antimicrobial resistance from different angles. Areas addressed inc lude mechanisms underlying this resistance, improved methods to detect resi stance when it occurs, alternate options for the treatment of infections ca used by resistant organisms, and strategies to prevent and control the emer gence and spread of resistance. In this review, the mode of action of antif ungals and their mechanisms of resistance are discussed. Additionally, an a ttempt is made to discuss the correlation between fungal and bacterial resi stance. Antifungals can be grouped into three classes based on their site o f action: azoles, which inhibit the synthesis of ergosterol (the main funga l sterol); polyenes, which interact with fungal membrane sterols physicoche mically; and 5-fluorocytosine, which inhibits macromolecular synthesis. Man y different types of mechanisms contribute to the development of resistance to antifungals. These mechanisms include alteration in drug target, altera tion in sterol biosynthesis, reduction in the intercellular concentration o f target enzyme, and overexpression of the antifungal drug target. Although the comparison between the mechanisms of resistance to antifungals and ant ibacterials is necessarily limited by several factors defined in the review , a correlation between the two exists. For example, modification of enzyme s which serve as targets for antimicrobial action and the involvement of me mbrane pumps in the extrusion of drugs are well characterized in both the e ukaryotic and prokaryotic cells.