The Wolbachia endosymbiont of Brugia malayi has an active phosphoglycerate mutase: a candidate target for anti-filarial therapies.
Phosphoglycerate mutases (PGM) interconvert 2- and 3-phosphoglycerate in the glycolytic and gluconeogenic pathways. A putative cofactor-independent phosphoglycerate mutase gene (iPGM) was identified in the genome sequence of the Wolbachia endosymbiont from the filarial nematode, Brugia malayi (wBm). Since iPGM has no sequence or structural similarity to the cofactor-dependent phosphoglycerate mutase (dPGM) found in mammals, it may represent an attractive Wolbachia drug target. In the present study, wBm-iPGM cloned and expressed in Escherichia coli was mostly insoluble and inactive. However, the protein was successfully produced in the yeast Kluyveromyces lactis and the purified recombinant wBm-iPGM showed typical PGM activity. Our results provide a foundation for further development of wBm-iPGM as a promising new drug target for novel anti-filarial therapies that selectively target the endosymbiont.
Foster
Jeremy M
JM
New England Biolabs, Inc., 240 County Road, Ipswich, MA 01938, USA.
Raverdy
Sylvine
S
Ganatra
Mehul B
MB
Colussi
Paul A
PA
Taron
Christopher H
CH
Carlow
Clotilde K S
CK
D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D017178:Brugia malayi / Q000382:microbiology*; D003001:Cloning, Molecular; D004926:Escherichia coli / Q000235:genetics; D015870:Gene Expression; D007716:Kluyveromyces / Q000235:genetics; D008969:Molecular Sequence Data; D009243:NAD / Q000378:metabolism; D010736:Phosphoglycerate Mutase / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D016415:Sequence Alignment; D020577:Wolbachia / Q000201:enzymology* / Q000235:genetics
D001426:Bacterial Proteins; D009243:NAD; D010736:Phosphoglycerate Mutase