The Wolbachia endosymbiont of Brugia malayi has an active pyruvate phosphate dikinase.
Genome analysis of the glycolytic/gluconeogenic pathway in the Wolbachia endosymbiont from the filarial parasite Brugia malayi (wBm) has revealed that wBm lacks pyruvate kinase (PK) and may instead utilize the enzyme pyruvate phosphate dikinase (PPDK; ATP:pyruvate, orthophosphate phosphotransferase, EC 2.7.9.1). PPDK catalyses the reversible conversion of AMP, PPi and phosphoenolpyruvate (PEP) into ATP, Pi and pyruvate. The glycolytic pathway of most organisms, including mammals, contains exclusively PK for the production of pyruvate from PEP. Therefore, the absence of PPDK in mammals makes the enzyme an attractive Wolbachia drug target. In the present study, we have cloned and expressed an active wBm-PPDK, thereby providing insight into the energy metabolism of the endosymbiont. Our results support the development of wBm-PPDK as a promising new drug target in an anti-symbiotic approach to controlling filarial infection.
Division of Parasitology, New England Biolabs, 240 County Road, Ipswich, MA 01938, USA.
Sylvine
S
Raverdy
Jeremy M
JM
Foster
Erica
E
Roopenian
Clotilde K S
CK
Carlow
D000595:Amino Acid Sequence; D000818:Animals; D017178:Brugia malayi / Q000382:microbiology*; D003001:Cloning, Molecular; D015870:Gene Expression; D008969:Molecular Sequence Data; D010802:Phylogeny; D011772:Pyruvate, Orthophosphate Dikinase / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D020577:Wolbachia / Q000201:enzymology* / Q000235:genetics
D011772:Pyruvate, Orthophosphate Dikinase