Screening for potential prophylactics targeting sporozoite motility through the skin

Malaria Journal
Ross G DouglasFriedrich Frischknecht

Abstract

Anti-malarial compounds have not yet been identified that target the first obligatory step of infection in humans: the migration of Plasmodium sporozoites in the host dermis. This movement is essential to find and invade a blood vessel in order to be passively transported to the liver. Here, an imaging screening pipeline was established to screen for compounds capable of inhibiting extracellular sporozoites. Sporozoites expressing the green fluorescent protein were isolated from infected Anopheles mosquitoes, incubated with compounds from two libraries (MMV Malaria Box and a FDA-approved library) and imaged. Effects on in vitro motility or morphology were scored. In vivo efficacy of a candidate drug was investigated by treating mice ears with a gel prior to infectious mosquito bites. Motility was analysed by in vivo imaging and the progress of infection was monitored by daily blood smears. Several compounds had a pronounced effect on in vitro sporozoite gliding or morphology. Notably, monensin sodium potently affected sporozoite movement while gramicidin S resulted in rounding up of sporozoites. However, pre-treatment of mice with a topical gel containing gramicidin did not reduce sporozoite motility and infection. This approac...Continue Reading

References

Oct 1, 1974·The Journal of protozoology·J P Vanderberg
Aug 1, 1971·Proceedings of the National Academy of Sciences of the United States of America·D W UrryD F Mayers
Apr 1, 1993·Biophysical Journal·S A Seoh, D Busath
Mar 1, 1997·Antimicrobial Agents and Chemotherapy·C GumilaH J Vial
Aug 1, 1997·Antimicrobial Agents and Chemotherapy·M A Otten-KuipersJ A Op den Kamp
Nov 5, 1997·The American Journal of Tropical Medicine and Hygiene·S Sidjanski, J P Vanderberg
May 22, 2002·The Journal of Experimental Medicine·Tohru KariuYasuo Chinzei
Jun 10, 2004·Cellular Microbiology·Friedrich FrischknechtRobert Ménard
Jun 24, 2005·Infection and Immunity·Darcy L Medica, Photini Sinnis
Jan 24, 2006·Nature Medicine·Rogerio AminoRobert Ménard
Mar 30, 2006·Antimicrobial Agents and Chemotherapy·Audrey GegoDominique Mazier
Jan 17, 2007·Cellular Microbiology·Lucy Megumi YamauchiPhotini Sinnis
May 29, 2008·Future Microbiology·Photini Sinnis, Fidel Zavala
Jun 27, 2008·Proceedings of the National Academy of Sciences of the United States of America·David PlouffeElizabeth A Winzeler
Sep 18, 2008·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Sarah KüchlerKlaus D Kramer
Dec 23, 2008·Trends in Parasitology·Belinda J MorahanRoss L Coppel
Sep 26, 2009·PLoS Pathogens·Robert W MoonOliver Billker
Nov 27, 2009·The Journal of Biological Chemistry·Adebola FalaePurnima Bhanot
Dec 17, 2009·Cell Host & Microbe·Sylvia MünterFriedrich Frischknecht
Feb 18, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Stephan HeggeFriedrich Frischknecht
May 21, 2010·Nature·Francisco-Javier GamoJose F Garcia-Bustos
May 21, 2010·Nature·W Armand GuiguemdeR Kiplin Guy
May 25, 2010·Experimental Parasitology·Ricardo Leitao, Ana Rodriguez
Jun 24, 2011·PLoS Pathogens·Janina Kristin HellmannFriedrich Frischknecht
Jul 13, 2011·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Eric H EklandDavid A Fidock
Oct 28, 2011·The Physician and Sportsmedicine·Karrie Marren
Mar 8, 2012·The Journal of Infectious Diseases·Filipa P da CruzMiguel Prudêncio
Mar 23, 2012·ChemMedChem·Emily R DerbyshireJon Clardy
May 16, 2012·Proceedings of the National Academy of Sciences of the United States of America·Emily R DerbyshireJon Clardy
Oct 12, 2012·Seminars in Immunopathology·Photini Sinnis, Fidel Zavala
Nov 28, 2012·Skin Pharmacology and Physiology·W Wigger-AlbertiH C Korting
Apr 24, 2013·The Journal of Experimental Medicine·Joana TavaresRogerio Amino
Jun 8, 2013·Malaria Journal·Jeremy N BurrowsTimothy N C Wells
Jun 27, 2013·PloS One·Thomas SpangenbergPaul Willis
Nov 13, 2013·Nature Reviews. Microbiology·Erika L FlanneryElizabeth A Winzeler

❮ Previous
Next ❯

Citations

Mar 6, 2021·EMBO Molecular Medicine·Johanna RippFriedrich Frischknecht

❮ Previous
Next ❯

Software Mentioned

ToAST
SOLAS
GV

Related Concepts

Related Feeds

Antimalarial Agents (ASM)

Antimalarial agents, also known as antimalarials, are designed to prevent or cure malaria. Discover the latest research on antimalarial agents here.

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.

Antimalarial Agents

Antimalarial agents, also known as antimalarials, are designed to prevent or cure malaria. Discover the latest research on antimalarial agents here.