Elucidating the mechanisms and functions of bacterial-derived mediators on Plasmodium falciparum.

Some bacteria species in the mosquito midgut demonstrate anti-Plasmodial effect independent of the mosquito immune system.

Understanding this mechanism could help propose bacteria-mediated strategies for targeting and blocking transmission without producing transgenic bacteria.

This project proposes to identify mosquito midgut bacteria that secrete anti-parasitic factors and investigate their variations in natural Anopheles mosquito populations.

Mosquito stages of P. falciparum will be exposed to spent culture media of midgut bacteria species through in vitro and in vivo (using axenic mosquitoes) assays and developmental and functional parasite effects assessed by immunofluorescence microscopy.

The biological significance of the bacteria secreted products will be confirmed by comparing with parasite exposure to bacteria cells.

The natural prevalence of effective bacteria will be investigated in blood-fed field-caught Anopheles malaria vector species from areas of high and low malaria transmission using 16S sequencing.

In addition, bacterial metabolites will be identified by LC MS/MS for further investigations into their mechanisms of cell activity.

It is expected that results from this study will increase our knowledge in the biological role of specific bacteria in natural variations of vector competence and reveal bacterial products from mosquito microbiome that can be further explored for parasite transmission-blocking in the mosquitoes.