期刊
CELLULAR MICROBIOLOGY
卷 20, 期 1, 页码 -出版社
WILEY
DOI: 10.1111/cmi.12794
关键词
cyst; energy metabolism; lactate fermentation; LDH; Toxoplasma gondii; virulence
资金
- National Natural Science Foundation of China [31572508]
- The Natural Science Foundation of Hubei Province [2017CFA020]
- Fundamental Research Funds for the Central Universities in China [2662015PY048]
Glycolysis was thought to be the major pathway of energy supply in both fast-replicating tachyzoites and slowly growing bradyzoites of Toxoplasma gondii. However, its biological significance has not been clearly verified. The genome of T.gondii encodes two lactate dehydrogenases (LDHs), which are differentially expressed in tachyzoites and bradyzoites. 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, ldh1 and ldh1 ldh2 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 ldh1 ldh2 mutants replicated significantly more slowly than wild-type parasites when cultured under conditions with physiological levels of oxygen (3%). In addition, ldh1 ldh2 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.
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