Discussion

Tiago Donatelli Serafim, Iliano V. Coutinho-Abreu, Fabiano Oliveira, Claudio Meneses, Shaden Kamhawi and Jesus G. Valenzuela.

Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852, USA.

Disease vectors transmit pathogens as they blood feed, and most vectors take multiple blood meals during their lifetime. Here, we show a remarkable ramification of a subsequent uninfected blood meal for a Leishmania-infected sand fly. Within 24h after uninfected blood feeding by a sand fly carrying a mature infection, 93% of Leishmania metacyclics, previously considered a terminally differentiated infectious stage, dedifferentiate to a replicative form we term "retroleptomonad". This new replicative phase results in an amplification of metacyclics, and reveals an unidentified recurrent metacyclogenesis cycle that increases sand fly infectivity with every blood meal, including non-infectious blood meals. On the other hand, in the absence of a second blood meal the majority of Leishmania infections acquired by feeding on an infected host are lost. Together, these findings highlight the relevance of multiple blood meals for vector-borne pathogens that exceed facilitation of contact between insect and host. They reveal a novel and fundamental role for multiple blood meals in establishing the pathogen, and most importantly in perpetually enhancing infectivity of the insect vector. These findings also place readily available blood sources as a critical element of vector-borne pathogen transmission, a new concept of consequence for vector-borne diseases.