title: 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.
  
  
  
  Leishmania infantum, a parasitic protozoan causing fatal visceral leishmaniasis, is transmitted to humans through the bite of the sand fly Lutzomyia longipalpis Development of the parasite to its virulent metacyclic state occurs in the sand fly gut. In this study, the microbiota within the Lu. longipalpis midgut was delineated by 16S ribosomal DNA (rDNA) sequencing, revealing a highly diverse community composition that lost diversity as parasites developed to their metacyclic state and increased in abundance in infected flies. Perturbing sand fly gut microbiota with an antibiotic cocktail, which alone had no effect on either the parasite or the fly, arrested both the development of virulent parasites and parasite expansion. These findings indicate the importance of bacterial commensals within the insect vector for the development of virulent pathogens, and raise the possibility that impairing the microbial composition within the vector might represent a novel approach to control of vector-borne diseases.
authors.affiliation: Departments of Microbiology, Internal Medicine and Epidemiology, University of Iowa, Iowa City, Iowa, USA.
authors.forename: Patrick H
authors.initials: PH
authors.lastname: Kelly
authors.affiliation: Departments of Microbiology, Internal Medicine and Epidemiology, University of Iowa, Iowa City, Iowa, USA.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Bahr
authors.affiliation: Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, USA.
authors.forename: Tiago D
authors.initials: TD
authors.lastname: Serafim
authors.affiliation: Department of Molecular Virology and Microbiology, Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Nadim J
authors.initials: NJ
authors.lastname: Ajami
authors.affiliation: Department of Molecular Virology and Microbiology, Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Petrosino
authors.affiliation: Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, USA.
authors.forename: Claudio
authors.initials: C
authors.lastname: Meneses
authors.affiliation: Departments of Microbiology, Internal Medicine and Epidemiology, University of Iowa, Iowa City, Iowa, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Kirby
authors.affiliation: Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, USA.
authors.forename: Jesus G
authors.initials: JG
authors.lastname: Valenzuela
authors.affiliation: Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, USA.
authors.forename: Shaden
authors.initials: S
authors.lastname: Kamhawi
authors.affiliation: Departments of Microbiology, Internal Medicine and Epidemiology, University of Iowa, Iowa City, Iowa, USA mary-wilson@uiowa.edu.|Iowa City Veterans' Affairs Medical Center, Iowa City, Iowa, USA.
authors.forename: Mary E
authors.identifier: 0000-0001-8680-7275
authors.initials: ME
authors.lastname: Wilson
mesh_terms: D000818:Animals; D001419:Bacteria / Q000145:classification / Q000235:genetics; D002470:Cell Survival; D004275:DNA, Ribosomal / Q000737:chemistry / Q000235:genetics; D004199:Disease Vectors; D000069196:Gastrointestinal Microbiome; D018314:Leishmania infantum / Q000502:physiology*; D011576:Psychodidae / Q000382:microbiology*; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D017422:Sequence Analysis, DNA
chemical_list: D004275:DNA, Ribosomal; D012336:RNA, Ribosomal, 16S