Population changes induced in Candida albicans by nalidixic acid

Area of Science:

• Microbiology
• Molecular Biology
• Genetics

Background:

• Candida albicans exhibits varied responses to nalidixic acid (Nal), including death, tolerance, and resistance.
• The cellular response to Nal is influenced by growth phase, nutrient availability, and temperature.
• Nal is known to induce mutations, but its specific effects on C. albicans require detailed investigation.

Purpose of the Study:

• To elucidate the mechanisms underlying nalidixic acid-induced cellular responses in Candida albicans.
• To investigate the role of mitochondrial integrity and macromolecular synthesis in Nal-induced inactivation and mutation.
• To explore the conditions favoring Nal-resistance mutations and their characteristics.

Main Methods:

• Exposure of Candida albicans to nalidixic acid under varying nutritional and temperature conditions.
• Assessment of cell viability, physiological adaptation (tolerance), and mutation frequency to Nal-resistance.
• Analysis of Nal-resistant mutants' characteristics, including colony morphology, respiration, and sensitivity to inhibitors.
• Investigation of the effects of mitochondrial inhibitors (chloramphenicol, erythromycin) and DNA-intercalating agents (acriflavin, ethidium bromide) on Nal-induced responses.

Main Results:

• Nalidixic acid induces high-frequency Nal-resistant mutants specifically at 37°C with glucose and certain amino acids.
• Nal-induced cell death and mutation are prevented by chloramphenicol or erythromycin, suggesting mitochondrial involvement.
• Adaptation to Nal-tolerance is not affected by these mitochondrial inhibitors.
• Nal-resistant mutants exhibit altered mitochondrial function and high spontaneous reversion rates.
• Pre-growth with acriflavin or ethidium bromide enhances resistance to Nal-induced inactivation.

Conclusions:

• Nalidixic acid-induced cell inactivation and mutation in Candida albicans are primarily due to mitochondrial damage.
• Mitochondrial macromolecular synthesis plays a critical role in fixing or promoting this damage.
• Adaptation to Nal-tolerance operates via a different, non-mitochondrial mechanism.
• Findings have implications for the therapeutic application of nalidixic acid, particularly concerning its mutagenic potential.