Conference Agenda
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CP8: Drugs & Drug Resistance 1 - 10 min talks Location: Lecture Theatre 1 Session Chair: Christopher Hart, Griffith University Session Chair: Hannah Smith, Griffith University | |
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Effects of endochin-like quinolones (ELQs) on Toxoplasma gondii infection and responses of human retinal pigment epithelial cells: implications for the treatment of ocular toxoplasmosis 1: Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide, Australia; 2: College of Science and Engineering, Flinders University, Adelaide, Australia; 3: ARC Training Centre for Biofilm Research and Innovation, Flinders University, Adelaide, Australia; 4: School of Medicine, Division of Infectious Diseases, Oregon Health & Science University, Portland, Oregon, USA Toxoplasma gondii causes ocular toxoplasmosis, a vision-threatening retinal infection. Current therapeutics are not curative. ELQs are promising drugs not yet evaluated for ocular toxoplasmosis. Human retinal pigment epithelial cells (ARPE-19 line) were infected with T. gondii GT-1 or GPHT tachyzoites and treated with ELQ-316 or ELQ-685. Tachyzoite growth 50% inhibitory concentrations (IC50s) were calculated. Tachyzoite invasion, replication, and egress were assayed. Cell viability was evaluated by XTT assay. Cell response transcripts were measured by RT-qPCR. ELQ IC50s for GT-1 and GPHT were nanomolar-range and approximately equivalent (ELQ-316: 22.96±4.33nM vs. 21.23±3.92nM; ELQ-685: 1.08±0.34nM vs. 0.88±0.20nM; unpaired t-test, p>0.05). Both treatments significantly reduced replication (tachyzoites/rosette: ELQs ≤1.77±0.07 vs. untreated ≥6.85±0.66, p<0.0001; one-way ANOVA). Tachyzoite invasion and egress were not impacted by either drug. ELQs ≤12µM did not reduce cell viability (mitochondrial respiration (arbitrary units): ELQ 12µM 2.37±0.13 vs. untreated 2.19±0.07; p>0.05; one-way ANOVA). In GT-1-infected cells, ELQ treatment reduced 7 transcripts (CCL2, CXCL8, ICAM1, IL1B, IL6, NFKB1, PDCD1LG2; p≤0.0042) and increased 3 transcripts (CXCL10, TGFB2, VCAM1; p≤0.0048), versus untreated controls (one-way ANOVA). In GPHT-infected cells, ELQ treatment reduced 5 transcripts (CXCL8, ICAM1, IL6, NFKB1, REL; p≤0.043). ELQs were non-toxic in ARPE-19 cells, reduced T. gondii replication, and altered host inflammatory mediator expression. | |