Abstract
Abstract
Background
Visceral leishmaniasis (VL) is caused by
Leishmania donovani
and differentiates under the influence of biotope-specific gut bacteria in the
Leishmania donovani
-transmitting sand fly vector,
Phlebotomus argentipes,
which coexists with the
Leishmania donovani
-non-transmitting
Sergentomyia
species in the Indian subcontinent.
Hypothesis
Sergentomyia
are primarily herpetophilic. Interestingly, we identified a specific population of anthropophilic
Sergentomyia babu babu
, a proven naturally non-competent vector for transmitting
Leishmania donovani
, with high abundance and human-bite incidences in VL-non-endemic regions, compared with VL-endemic regions of India. Thus, the possibility of egesting gut bacteria to humans from VL-non-transmitting
Sergentomyia
and inducing downstream immune cascades remains undeniable.
Innovation
We characterized gut bacteria from anthropophilic
Sergentomyia babu babu
in both VL-endemic and VL-non-endemic regions of India and found that a heat-inactivated formulation of
Heyndrickxia sporothermodurans
[NCBI Sequence Read Archive (SRA): PRJNA1403236], isolated from anthropophilic
Sergentomyia babu babu
from a VL-non-endemic region, prevented and cured
L. donovani
infection by inducing IL-23∼Th17. More importantly, it also prevented the initial parasite establishment by inducing phagocytosis, ROS, and TNF-α in circulatory Ly6G
−
CD11b
+
Ly6C
hi
monocytes. To the best of our knowledge, this is the first report confirming that the gut bacteria of VL-non-transmitting sand flies are critical and need to be investigated in depth for developing therapeutics and/or prophylactics against visceral leishmaniasis (VL), and suggests that possible bite-transfer of gut bacteria from disease-non-transmitting vectors to hosts may restrict disease pathogenicity. Further clinical trials are needed to warrant (Indian patent: 202511041013, April 28, 2025).