Leptomonas seymouri: Adaptations to the Dixenous Life Cycle Analyzed by Genome Sequencing, Transcriptome Profiling and Co-infection with Leishmania donovani

The co-infection cases involving dixenous Leishmania spp. (mostly of the L. donovani complex) and presumably monoxenous trypanosomatids in immunocompromised mammalian hosts including humans are well documented. The main opportunistic parasite has been identified as Leptomonas seymouri of the sub-family Leishmaniinae. The molecular mechanisms allowing a parasite of insects to withstand elevated temperature and substantially different conditions of vertebrate tissues are not understood. Here we demonstrate that L. seymouri is well adapted for the environment of the warm-blooded host. We sequenced the genome and compared the whole transcriptome profiles of this species cultivated at low and high temperatures (mimicking the vector and the vertebrate host, respectively) and identified genes and pathways differentially expressed under these experimental conditions. Moreover, Leptomonas seymouri was found to persist for several days in two species of Phlebotomus spp. implicated in Leishmania donovani transmission. Despite of all these adaptations, L. seymouri remains a predominantly monoxenous species not capable of infecting vertebrate cells under normal conditions.
Author Summary In this work we performed a comprehensive evaluation of the infective potential of Leptomonas seymouri, repeatedly isolated from kala-azar patients infected by Leishmania donovani in India and neighboring countries, and have tested the capacity of this monoxenous trypanosomatid to utilize the sand fly vectors permissive for Leishmania donovani. We concluded that despite several genetic adaptations it has developed, Leptomonas seymouri remains a predominantly monoxenous species not able to infect mammalian macrophages either alone or in co-infection with Leishmania. Under certain circumstances it is able to infect mammals, but probably only when the host is immunocompromised by infection with another pathogen, such as Leishmania donovani or HIV.