Campbell BE

References (4)

Title : Whole-genome sequence of Schistosoma haematobium - Young_2012_Nat.Genet_44_221
Author(s) : Young ND , Jex AR , Li B , Liu S , Yang L , Xiong Z , Li Y , Cantacessi C , Hall RS , Xu X , Chen F , Wu X , Zerlotini A , Oliveira G , Hofmann A , Zhang G , Fang X , Kang Y , Campbell BE , Loukas A , Ranganathan S , Rollinson D , Rinaldi G , Brindley PJ , Yang H , Wang J , Gasser RB
Ref : Nat Genet , 44 :221 , 2012
Abstract : Schistosomiasis is a neglected tropical disease caused by blood flukes (genus Schistosoma; schistosomes) and affecting 200 million people worldwide. No vaccines are available, and treatment relies on one drug, praziquantel. Schistosoma haematobium has come into the spotlight as a major cause of urogenital disease, as an agent linked to bladder cancer and as a predisposing factor for HIV/AIDS. The parasite is transmitted to humans from freshwater snails. Worms dwell in blood vessels and release eggs that become embedded in the bladder wall to elicit chronic immune-mediated disease and induce squamous cell carcinoma. Here we sequenced the 385-Mb genome of S. haematobium using Illumina-based technology at 74-fold coverage and compared it to sequences from related parasites. We included genome annotation based on function, gene ontology, networking and pathway mapping. This genome now provides an unprecedented resource for many fundamental research areas and shows great promise for the design of new disease interventions.
ESTHER : Young_2012_Nat.Genet_44_221
PubMedSearch : Young_2012_Nat.Genet_44_221
PubMedID: 22246508
Gene_locus related to this paper: schha-ACHE , schha-a0a094zs51 , schha-a0a095agr4 , schha-a0a095ai61 , schha-a0a095ayl3 , schha-a0a095c2i3 , schha-a0a095ce64

Title : Hydrolysis of pyrethroids by carboxylesterases from Lucilia cuprina and Drosophila melanogaster with active sites modified by in vitro mutagenesis - Heidari_2005_Insect.Biochem.Mol.Biol_35_597
Author(s) : Heidari R , Devonshire AL , Campbell BE , Dorrian SJ , Oakeshott JG , Russell RJ
Ref : Insect Biochemistry & Molecular Biology , 35 :597 , 2005
Abstract : The cloned genes encoding carboxylesterase E3 in the blowfly Lucilia cuprina and its orthologue in Drosophila melanogaster were expressed in Sf9 cells transfected with recombinant baculovirus. Resistance of L. cuprina to organophosphorus insecticides is due to mutations in the E3 gene that enhance the enzyme's ability to hydrolyse insecticides. Previous in vitro mutagenesis and expression of these modifications (G137D, in the oxyanion hole and W251L, in the acyl pocket) have confirmed their functional significance. We have systematically substituted these and nearby amino acids by others expected to affect the hydrolysis of pyrethroid insecticides. Most mutations of G137 markedly decreased pyrethroid hydrolysis. W251L was the most effective of five substitutions at this position. It increased activity with trans permethrin 10-fold, and the more insecticidal cis permethrin >130-fold, thereby decreasing the trans:cis hydrolysis ratio to only 2, compared with >25 in the wild-type enzyme. Other mutations near the bottom of the catalytic cleft generally enhanced pyrethroid hydrolysis, the most effective being F309L, also in the presumptive acyl binding pocket, which enhanced trans permethrin hydrolysis even more than W251L. In these assays with racemic 1RS cis and 1RS trans permethrin, two phases were apparent, one being much faster suggesting preferential hydrolysis of one enantiomer in each pair as found previously with other esterases. Complementary assays with individual enantiomers of deltamethrin and the dibromo analogue of cis permethrin showed that the wild type and most mutants showed a marked preference for the least insecticidal 1S configuration, but this was reversed by the F309L substitution. The W251L/F309L double mutant was best overall in hydrolysing the most insecticidal 1R cis isomers. The results are discussed in relation to likely steric effects on enzyme-substrate interactions, cross-resistance between pyrethroids and malathion, and the potential for bioremediation of pyrethroid residues.
ESTHER : Heidari_2005_Insect.Biochem.Mol.Biol_35_597
PubMedSearch : Heidari_2005_Insect.Biochem.Mol.Biol_35_597
PubMedID: 15857765
Gene_locus related to this paper: drome-EST23aes07 , luccu-E3aest7

Title : Hydrolysis of organophosphorus insecticides by in vitro modified carboxylesterase E3 from Lucilia cuprina - Heidari_2004_Insect.Biochem.Mol.Biol_34_353
Author(s) : Heidari R , Devonshire AL , Campbell BE , Bell KL , Dorrian SJ , Oakeshott JG , Russell RJ
Ref : Insect Biochemistry & Molecular Biology , 34 :353 , 2004
Abstract : Resistance of the blowfly, Lucilia cuprina, to organophosphorus (OP) insecticides is due to mutations in LcalphaE7, the gene encoding carboxylesterase E3, that enhance the enzyme's ability to hydrolyse insecticides. Two mutations occur naturally, G137D in the oxyanion hole of the esterase, and W251L in the acyl binding pocket. Previous in vitro mutagenesis and expression of these modifications to the cloned gene have confirmed their functional significance. G137D enhances hydrolysis of diethyl and dimethyl phosphates by 55- and 33-fold, respectively. W251L increases dimethyl phosphate hydrolysis similarly, but only 10-fold for the diethyl homolog; unlike G137D however, it also retains ability to hydrolyse carboxylesters in the leaving group of malathion (malathion carboxylesterase, MCE), conferring strong resistance to this compound. In the present work, we substituted these and nearby amino acids by others expected to affect the efficiency of the enzyme. Changing G137 to glutamate or histidine was less effective than aspartate in improving OP hydrolase activity and like G137D, it diminished MCE activity, primarily through increases in Km. Various substitutions of W251 to other smaller residues had a broadly similar effect to W251L on OP hydrolase and MCE activities, but at least two were quantitatively better in kinetic parameters relating to malathion resistance. One, W251G, which occurs naturally in a malathion resistant hymenopterous parasitoid, improved MCE activity more than 20-fold. Mutations at other sites near the bottom of the catalytic cleft generally diminished OP hydrolase and MCE activities but one, F309L, also yielded some improvements in OP hydrolase activities. The results are discussed in relation to likely steric effects on enzyme-substrate interactions and future evolution of this gene.
ESTHER : Heidari_2004_Insect.Biochem.Mol.Biol_34_353
PubMedSearch : Heidari_2004_Insect.Biochem.Mol.Biol_34_353
PubMedID: 15041019
Gene_locus related to this paper: luccu-E3aest7

Title : Kinetic efficiency of mutant carboxylesterases implicated in organophosphate insecticide resistance - Devonshire_2003_Pestic.Biochem.Physiol_76_1
Author(s) : Devonshire AL , Heidari R , Bell KL , Campbell PM , Campbell BE , Odgers WA , Oakeshott JG , Russell RJ
Ref : Pesticide Biochemistry and Physiology , 76 :1 , 2003
Abstract : Resistance to organophosphorus (OP) insecticides in Lucilia cuprina arises from two mutations in carboxylesterase E3 that enable it to hydrolyse the phosphate ester of various organophosphates, plus the carboxlyester in the leaving group in the case of malathion. These mutations are not found naturally in the orthologous EST23 enzyme in Drosophila melanogaster. We have introduced the two mutations (G137D and W251L) into cloned genes encoding E3 and EST23 from susceptible L. cuprina and D. melanogaster and expressed them in vitro with the baculovirus system. The ability of the resultant enzymes to hydrolyse the phosphate ester of diethyl and dimethyl organophosphates was studied by a novel fluorometric assay, which also provided a sensitive titration technique for the molar amount of esterase regardless of its ability to hydrolyse the fluorogenic substrate used. Malathion carboxylesterase activity was also measured. The G137D mutation markedly enhanced (>30-fold) hydrolysis of both classes of phosphate ester by E3 but only had a similar effect on the hydrolysis of dimethyl organophosphate in EST23. Introduction of the W251L mutation into either gene enhanced dimethyl (23-30-fold) more than diethyl (6-10-fold) organophosphate hydrolysis and slightly improved (2-4-fold) malathion carboxylesterase activity, but only at high substrate concentration.
ESTHER : Devonshire_2003_Pestic.Biochem.Physiol_76_1
PubMedSearch : Devonshire_2003_Pestic.Biochem.Physiol_76_1
PubMedID:
Gene_locus related to this paper: luccu-E3aest7 , musdo-EST23aes07