Fighting malaria with engineered symbiotic bacteria from vector mosquitoes

Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12734-9. doi: 10.1073/pnas.1204158109. Epub 2012 Jul 16.


The most vulnerable stages of Plasmodium development occur in the lumen of the mosquito midgut, a compartment shared with symbiotic bacteria. Here, we describe a strategy that uses symbiotic bacteria to deliver antimalaria effector molecules to the midgut lumen, thus rendering host mosquitoes refractory to malaria infection. The Escherichia coli hemolysin A secretion system was used to promote the secretion of a variety of anti-Plasmodium effector proteins by Pantoea agglomerans, a common mosquito symbiotic bacterium. These engineered P. agglomerans strains inhibited development of the human malaria parasite Plasmodium falciparum and rodent malaria parasite Plasmodium berghei by up to 98%. Significantly, the proportion of mosquitoes carrying parasites (prevalence) decreased by up to 84% for two of the effector molecules, scorpine, a potent antiplasmodial peptide and (EPIP)(4), four copies of Plasmodium enolase-plasminogen interaction peptide that prevents plasminogen binding to the ookinete surface. We demonstrate the use of an engineered symbiotic bacterium to interfere with the development of P. falciparum in the mosquito. These findings provide the foundation for the use of genetically modified symbiotic bacteria as a powerful tool to combat malaria.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anopheles* / metabolism
  • Anopheles* / microbiology
  • Anopheles* / parasitology
  • Antimalarials / metabolism*
  • Bacterial Secretion Systems / genetics
  • Escherichia coli Proteins / biosynthesis*
  • Escherichia coli Proteins / genetics
  • Hemolysin Proteins / biosynthesis*
  • Hemolysin Proteins / genetics
  • Insect Vectors* / immunology
  • Insect Vectors* / parasitology
  • Malaria, Falciparum / metabolism
  • Malaria, Falciparum / prevention & control*
  • Pantoea / genetics
  • Pantoea / metabolism*
  • Plasmodium berghei*
  • Plasmodium falciparum*
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / genetics
  • Symbiosis


  • Antimalarials
  • Bacterial Secretion Systems
  • Escherichia coli Proteins
  • Hemolysin Proteins
  • Recombinant Proteins