The Gut Microbiome of the Vector Lutzomyia longipalpis Is Essential for Survival of Leishmania infantum

Abstract

The vector-borne disease leishmaniasis, caused by Leishmania species protozoa, is transmitted to humans by phlebotomine sand flies. Development of Leishmania to infective metacyclic promastigotes in the insect gut, a process termed metacyclogenesis, is an essential prerequisite for transmission. Based on the hypothesis that vector gut microbiota influence the development of virulent parasites, we sequenced midgut microbiomes in the sand fly Lutzomyia longipalpis with or without Leishmania infantum infection. Sucrose-fed sand flies contained a highly diverse, stable midgut microbiome. Blood feeding caused a decrease in microbial richness that eventually recovered. However, bacterial richness progressively decreased in L. infantum-infected sand flies. Acetobacteraceae spp. became dominant and numbers of Pseudomonadaceae spp. diminished coordinately as the parasite underwent metacyclogenesis and parasite numbers increased. Importantly, antibiotic-mediated perturbation of the midgut microbiome rendered sand flies unable to support parasite growth and metacyclogenesis. Together, these data suggest that the sand fly midgut microbiome is a critical factor for Leishmania growth and differentiation to its infective state prior to disease transmission.

The midgut microbiota plays an essential role in sand fly vector competence forLeishmania major

“…Our findings confirm a recent study involving another Leishmania species ( L. infantum ), and another vector ( L. longipalpis ), in which dysbiosis of the midgut also resulted in promastigote killing and failure to generate metacyclics (Kelly et al, ). No attempts were made to rescue the parasites using feeds on live bacteria or bacterial products or to localise the killing to different midgut microenvironments, so it is not clear if the bacteria are contributing the same benefit to Leishmania survival as we report here.…”

“…One conclusion from these studies is that any manipulation that reduces the size and/or diversity of the natural microbiota should enhance the ability of Leishmania to establish infections in the fly, similar to the increased susceptibility to Plasmodium faliciparum or to dengue virus infection observed in antibiotic‐treated Anopheles gambiae or Aedes aegypti mosquitoes, respectively (Dong, Manfredini, & Dimopoulos, ; Xi, Ramirez, & Dimopoulos, ). It was therefore surprising that antibiotic treatment of L. longipalpis sand flies was recently shown to severely restrict their ability to support the growth and differentiation of Leishmania infantum (Kelly et al, ). In the current studies, our attempts to exploit antibiotic treatment of colonised P. duboscqi sand flies in order to improve their vector competency for L. major resulted instead in flies that were highly refractory to the development of transmissible infections.…”

Comparative analysis of microbial community in the whole body and midgut from fully engorged and unfed female adult Melophagus ovinus

“…The bacterial community of insect vectors is easily affected by blood‐feeding behaviour that may cause the bacterial diversity of vectors to increase or decrease (Wang et al ., ; Nayduch et al ., ; Kelly et al ., ; Varela‐Stokes et al ., ; Telleria et al ., ). In the present study, whole‐body samples from newly hatched and unfed adult female M. ovinus showed the highest bacterial diversity.…”

Leishmania infection induces a limited differential gene expression in the sand fly midgut

“…These findings also suggest that other factors not controlled for by the experimental design accounted for the variance observed in PC2. Along these lines, it is noteworthy that Leishmania infection in sand fly midguts also modify the microbiota composition [17], which may also have affected gene expression in the midgut samples.…”