Functional analysis of Toxoplasma lactate dehydrogenases suggests critical roles of lactate fermentation for parasite growth in vivo

In this study, we knocked out the two LDH genes individually and in combination, and found that neither gene was required for tachyzoite growth in vitro under standard growth conditions. However during infection in mice, Δldh1 and Δldh1 Δldh2 mutants were unable to propagate and displayed significant virulence attenuation and cyst formation defects. LDH2 only played minor roles in these processes. To further elucidate the mechanisms underlying the critical requirement of LDH in vivo, we found that Δldh1 Δldh2 mutants replicated significantly more slowly than wild type parasites when cultured under conditions with physiological levels of oxygen (3%). In addition, Δldh1 Δldh2 mutants were more susceptible to the oxidative phosphorylation inhibitor oligomycin A. Together these results suggest that lactate fermentation is critical for parasite growth under physiological conditions, likely because energy production from oxidative phosphorylation is insufficient when oxygen is limited and lactate fermentation becomes a key supplementation.

Source: Cellular Microbiology - October 13, 2017 Category: Microbiology Authors: Ningbo Xia, Jichao Yang, Shu Ye, Lihong Zhang, Yanqin Zhou, Junlong Zhao, L. David Sibley, Bang Shen Tags: RESEARCH ARTICLE Source Type: research