Letter | Published:

Sequential blood meals promote Leishmania replication and reverse metacyclogenesis augmenting vector infectivity

Nature Microbiologyvolume 3pages548555 (2018) | Download Citation


Sand flies, similar to most vectors, take multiple blood meals during their lifetime1,2,3,4. The effect of subsequent blood meals on pathogens developing in the vector and their impact on disease transmission have never been examined. Here, we show that ingestion of a second uninfected blood meal by Leishmania-infected sand flies triggers dedifferentiation of metacyclic promastigotes, considered a terminally differentiated stage inside the vector5, to a leptomonad-like stage, the retroleptomonad promastigote. Reverse metacyclogenesis occurs after every subsequent blood meal where retroleptomonad promastigotes rapidly multiply and differentiate to metacyclic promastigotes enhancing sand fly infectiousness. Importantly, a subsequent blood meal amplifies the few Leishmania parasites acquired by feeding on infected hosts by 125-fold, and increases lesion frequency by fourfold, in twice-fed compared with single-fed flies. These findings place readily available blood sources as a critical element in transmission and propagation of vector-borne pathogens.

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We would like to thank E. Fischer and S. Ricklefs from the Research Technology Branch (RTB), NIAID, for electron microscopy support; R. Kissinger from RTB, NIAID, for illustration support; A. Perkins and W. de Castro from VMBS, NIAID, for technical support; V. Vernyuy, T.R. Wilson and B.G. Bonilla from LMVR, NIAID for sand fly insectary support; R. Dey and H. Nakhasi from CBER, FDA, for help with qPCR; A.M.A. Souza for help with statistical analysis and C. Barillas-Mury and J.M.C. Ribeiro from LMVR, NIAID, for critical reading of the manuscript. This research was supported by the Intramural Research Program of the NIH, National Institute of Allergy and Infectious Diseases.

Author information


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

    • Tiago D. Serafim
    • , Iliano V. Coutinho-Abreu
    • , Fabiano Oliveira
    • , Claudio Meneses
    • , Shaden Kamhawi
    •  & Jesus G. Valenzuela


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T.D.S. and I.V.C.A. designed and performed the experiments. T.D.S. analysed the data. I.V.C.A analysed qPCR data. C.M. performed sand fly insectary work. J.G.V., S.K. and F.O. were involved in the design, interpretation and supervision of this study. All authors wrote the manuscript.

Competing interests

The authors declare no competing interests

Corresponding authors

Correspondence to Shaden Kamhawi or Jesus G. Valenzuela.

Supplementary information

  1. Supplementary Information

    Supplementary Figures 1–4. Supplementary Tables 1–3. Legends for Supplementary Videos 1–8.

  2. Life Sciences Reporting Summary(PDF 64 kb)


  1. Supplementary Video 1

    Fast-swimming metacyclics at mature infection.

  2. Supplementary Video 2

    Fast-swimming metacyclics at mature infection.

  3. Supplementary Video 3

    Fast-swimming metacyclics dedifferentiate into slow moving retroleptomonads after a subsequent uninfected blood meal.

  4. Supplementary Video 4

    Fast-swimming metacyclics dedifferentiate into slow moving retroleptomonads after a subsequent uninfected blood meal.

  5. Supplementary Video 5

    Dedifferentiation of a metacyclic promastigote – representative event 1.

  6. Supplementary Video 6

    Dedifferentiation of a metacyclic promastigote – representativeevent 2.

  7. Supplementary Video 7

    Dedifferentiation of a metacyclic promastigote – representativeevent 3.

  8. Supplementary Video 8

    The haptomonad parasite sphere of an infected sand fly after a subsequent uninfected blood meal.

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