Author
Temeyer, Kevin | |
TONG, FAN - University Of Florida | |
CHEN, QIAO-HONG - Virginia Tech | |
CARLIER, PAUL - Virginia Tech | |
Perez De Leon, Adalberto - Beto | |
BLOOMQUIST, JEFFREY - University Of Florida |
Submitted to: Meeting Abstract
Publication Type: Abstract Only Publication Acceptance Date: 6/19/2017 Publication Date: N/A Citation: N/A Interpretive Summary: Technical Abstract: Phlebotomine sand flies are small hematophagous vectors of human and zoonotic leishmaniases present throughout tropical and subtropical areas of the world. Phlebotomus papatasi is a principal vector of human cutaneous leishmaniasis that has presented serious problems for military operations and resident populations in the Middle East and other areas where they are endemic. The acetylcholinesterase (AChE) of P. papatasi (PpAChE) shares substantial sequence identity with AChE of Lutzomyia spp., the New World Sand Fly, as well as AChE1 of important mosquito species. We utilized targeted mutagenesis and baculovirus expression to produce and characterize recombinant PpAChEs containing mutations orthologous to those responsible for mosquito insensitivity to organophosphate. Biochemical properties of the rPpAChEs containing single amino acid substitutions included increased Michaelis–Menten constant (Km) and decreased sensitivity to organophosphate inhibition. Novel synthetic carbamates were screened to identify candidate compounds for improved efficacy. |