Efficacy of Linezolid as a Novel Therapeutic Agent against Toxoplasma gondii RH Strain: In Vitro and BALB/c Mouse Models

Toxoplasma gondii (T. gondii) is an important human and veterinary pathogen, and current therapies such as sulfadiazine and pyrimethamine may cause adverse effects. Identifying alternative treatments is therefore essential. This study aimed to evaluate the antiparasitic activity of the antibiotic linezolid against Toxoplasma gondii in vitro and in vivo.

Linezolid and standard drugs were prepared at concentrations ranging from 0.625 to 40 µg/mL and tested against tachyzoite using microscopic examination, cell viability assays, and flow cytometry. Cytotoxicity was assessed in HeLa cells. For the in vivo experiment, BALB/c mice were infected with T. gondii and treated with linezolid for 14 days. Survival was monitored and compared to untreated controls and to standard drug treatment.

Linezolid reduced tachyzoite counts in vitro in a time-dependent manner (p<0.05). The calculated IC50 was 12.4 µg/mL, while cytotoxicity on HeLa cells (CC50) was 92.3 µg/mL, indicating moderate selectivity (SI=7.4). Flow cytometry showed induction of early and late apoptosis in tachyzoites. In vivo, untreated mice died by day nine, while linezolid therapy prolonged survival to day eleven. Combination treatment with pyrimethamine and linezolid resulted in the longest survival, reaching day 13.

These findings suggest that linezolid inhibits parasite growth and triggers apoptotic death with limited toxicity to host cells. Although the in vivo survival benefit was modest and comparable to standard therapy, combination treatment enhanced overall efficacy.

Linezolid shows potential as an adjunct or alternative therapy for toxoplasmosis and warrants further investigation in optimized dosing regimens and combination approaches.