Researchers studying fungal pathogens isolated an ergosterol biosynthetic gene by polymerase chain reaction. Using homologous recombination, they then developed a new strain of Candida with a mutated allele for that gene. The mutant strain was cultured in the presence of several different antifungal agents. Compared to isolates from the wild-type strain, isolates from the mutant Candida strain exhibited enhanced growth in the presence of drug X. Further investigation revealed that the mechanism of resistance to drug X was a decrease in ergosterol incorporation into the cell membrane. Based on this data, drug X is likely to be most closely related to which of the following antifungal agents?

Question

Researchers studying fungal pathogens isolated an ergosterol biosynthetic gene by polymerase chain reaction.  Using homologous recombination, they then developed a new strain of Candida with a mutated allele for that gene.  The mutant strain was cultured in the presence of several different antifungal agents.  Compared to isolates from the wild-type strain, isolates from the mutant Candida strain exhibited enhanced growth in the presence of drug X.  Further investigation revealed that the mechanism of resistance to drug X was a decrease in ergosterol incorporation into the cell membrane.  Based on this data, drug X is likely to be most closely related to which of the following antifungal agents?

Quizplus · Accepted Answer

11ec160b_380b_ee11_9249_6b2adc11af39_MD0001_00 The main classes of antifungal medications currently in use include: Of these agents, only the polyenes (amphotericin B, nystatin) depend on the amount of ergosterol incorporated into fungal cell membranes for their efficacy. These drugs bind to ergosterol molecules, forming pores in the membrane and allowing leakage of ions (especially K⁺) from the cells. This disruption of cell membrane integrity leads to cell lysis. An organism that decreases the amount of ergosterol in its cell membrane would likely become resistant to polyenes. Amphotericin B is a systemic antifungal active against Candida, Aspergillus, Cryptococcus, Histoplasma, Blastomyces, and Coccidioides. Nystatin is used topically; oral candidiasis is the main indication for its use ("swish and swallow"). (Choice A) Caspofungin is an antifungal agent that blocks synthesis of the glucan component of the fungal cell wall. It is active against Candida and Aspergillus. Caspofungin does not bind ergosterol. (Choice B) Cyclosporine is an immunosuppressant used in transplant recipients to prevent rejection. It decreases the synthesis of IL-2, thereby inhibiting T cell proliferation. (Choice C) Flucytosine is used in combination with amphotericin B primarily for the treatment of cryptococcal meningitis in patients with HIV. It is a nucleotide analog that competitively inhibits RNA synthesis in fungal cells. (Choice D) Griseofulvin interacts with fungal cell microtubules, inhibiting mitosis. It accumulates in keratin-containing tissues and is used to treat dermatophyte infections (eg, Microsporum, Epidermophyton, Trichophyton). Educational objective: The main groups of antifungal drugs are polyenes, azoles, echinocandins, and pyrimidines. Polyene antifungals (eg, amphotericin B, nystatin) act by binding ergosterol in the fungal cell membrane.

Researchers Studying Fungal Pathogens Isolated an Ergosterol Biosynthetic Gene by Polymerase