II: FUNGI

E. Chemotherapeutic Control of Fungi

Fundamental Statements for this Learning Object:

1. Because fungi, like human cells, are eukaryotic, there are far fewer chemotherapeutic agents that are selectively toxic for fungi than there are for prokaryotic bacteria.
2. Most antifungal agents bind to or interfere with the synthesis of ergosterol, the sterol in their cytoplasmic membrane, altering membrane structure and function.

 

LEARNING OBJECTIVES FOR THIS SECTION

Mycology (def) is the study of fungi. Fungi include yeasts, molds, and fleshy fungi. They:

1. are eukaryotic;
2. have a rigid cell wall;
3. are chemoheterotrophs (organisms that require organic compounds for both carbon and energy sources);
4. obtain their nutrients by absorption;
5. obtain nutrients as saprophytes, organisms that live off of decaying matter, or as parasites, organisms that live off of living matter.

We will be concerned mainly with the yeasts and molds, especially those causing mycoses (fungal infections).

In this section we will look at the chemotherapeutic control of fungi.

Chemotherapeutic Control of Fungi

Remember that like human cells, fungal cells are eukaryotic. Since fungal cells, unlike prokaryotic bacterial cells, are not that different from human cells, it is more difficult to find a chemotherapeutic agent that is selectively toxic (def) for fungi, that is, will inhibit or kill fungal cells without also inhibiting or killing human cells. Some of the common antifungal chemotherapeutic agents are listed below.

1. One antibiotic, griseofulvin (Fulvicin, Grifulvin, Gris-PEG), interferes with nuclear division by preventing the aggregation of microtubules needed for mitosis in superficial mycelial fungi. It is used only for severe dermatophyte (def) infections.

2. The antimetabolites (def) trimethoprim + sulfomethoxazole , trimetrexate, atovaquone, and flucytosine interfere with normal nucleic acid synthesis. Trimethoprim/sulfomethoxazole (Septra, Bactrim), atovaquone (Mepron), and trimetrexate (Neutrexin) are used to treat Pneumocystis pneumonia. Flucytosine (Ancobon) is used for more serious Candida infections.

3. Polyene antibiotics such as amphotericin B, pimaricin, and nystatin are fungicidal drugs that bind to ergosterol (def) in the fungal cytoplasmic membrane thus altering its structure and function and causing leakage of cellular needs. Nystatin (Mycostatin) is used to treat superficial (def) Candida infections (thrush, vaginitis, cutaneous infections), amphotericin B (Abelcet, Fungizone) is used for systemic (def) Candida infections, Cryptococcus infections, and dimorphic fungal infections.

4. The azole derivative antibiotics such as clotrimazole, miconazole, itraconazole, fluconazole, and ketoconazole, are fungistatic drugs used to treat many fungal infections. They interfere with ergosterol biosynthesis and thus alter the structure of the cytoplasmic membrane as well as the function of several membrane-bound enzymes like those involved in nutrient transport and chitin synthesis.

Clotrimazole (Lotramin, Mycelex), miconazole (Monistat), and econazole (Spectazole) are used to treat superficial Candida and dermatophyte infections; oxiconazole (Oxistat) and sulconazole (Exelderm) are used for dermatophyte infections; butaconazole (Femstat-3), terconazole (Terazole), and tioconazole (Vagistat-1) are used for Candida vaginitis; ketoconazole (Nizoral) and itraconazole (Sporanox) are used for systemic Candida, Cryptococcus, and dimorphic fungal infections; and fluconazole (Diflucan) is used for Candida infections. Voriconazole (VFEND) is a triazole is used to treat Candida infections such as candidemia, disseminated infections in skin and infections in abdomen, kidney, bladder wall, and wounds. It is also used for invasive aspergillosis.

5. Echinocandins, including caspofungin (Cancidas) and micafungin (Mycamine) are intravenous antifungals that inhibits glucan synthesis in fungal cell walls. It is used in the treatment of candidemia , Candida intra-abdominal abscesses, peritonitis, esophageal candidiasis,  and pleural space infections.

6. Naftifine (Naftin) and terbinafine (Lamisil) are allylamines that block synthesis of ergosterol as does the topical thiocarbonate tolnaftate. They are used to treat dermatophyte infections.

TPS Question

 

For a more detailed description of any specific antimicrobial agent, see the website of RxList - The Internet Drug Index.

Gary E. Kaiser, Ph.D.
Professor of Microbiology
The Community College of Baltimore County, Catonsville Campus
This work is licensed under a Creative Commons Attribution 4.0 International License.
Based on a work The Grapes of Staph at https://cwoer.ccbcmd.edu/science/microbiology/index_gos.html.