4.7 Article

Chromobacterium Csp_P Reduces Malaria and Dengue Infection in Vector Mosquitoes and Has Entomopathogenic and In Vitro Anti-pathogen Activities

Journal

PLOS PATHOGENS
Volume 10, Issue 10, Pages -

Publisher

PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.ppat.1004398

Keywords

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Funding

  1. National Institutes of Health/National Institute for Allergy and Infectious Disease [1R01AI061576-01A1, RO1 AI059492, RO1AI078997]
  2. Johns Hopkins Malaria Research Institute
  3. Bloomberg Family Foundation
  4. individual F31 NRSA training grant from NIH/NIAID [1F31AI080161-01A1]
  5. American Society for Microbiology Robert D. Watkins Graduate Research Fellowship

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Plasmodium and dengue virus, the causative agents of the two most devastating vector-borne diseases, malaria and dengue, are transmitted by the two most important mosquito vectors, Anopheles gambiae and Aedes aegypti, respectively. Insect-bacteria associations have been shown to influence vector competence for human pathogens through multi-faceted actions that include the elicitation of the insect immune system, pathogen sequestration by microbes, and bacteria-produced anti-pathogenic factors. These influences make the mosquito microbiota highly interesting from a disease control perspective. Here we present a bacterium of the genus Chromobacterium (Csp_P), which was isolated from the midgut of field-caught Aedes aegypti. Csp_P can effectively colonize the mosquito midgut when introduced through an artificial nectar meal, and it also inhibits the growth of other members of the midgut microbiota. Csp_P colonization of the midgut tissue activates mosquito immune responses, and Csp_P exposure dramatically reduces the survival of both the larval and adult stages. Ingestion of Csp_P by the mosquito significantly reduces its susceptibility to Plasmodium falciparum and dengue virus infection, thereby compromising the mosquito's vector competence. This bacterium also exerts in vitro anti-Plasmodium and anti-dengue activities, which appear to be mediated through Csp_P-produced stable bioactive factors with transmission-blocking and therapeutic potential. The anti-pathogen and entomopathogenic properties of Csp_P render it a potential candidate for the development of malaria and dengue control strategies.

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