Brian L Weiss

Yale University | YU · Department of Epidemiology of Microbial Diseases

The primary vector of the trypanosome parasite causing human and animal African trypanosomiasis in Uganda is the riverine tsetse fly Glossina fuscipes fuscipes (Gff). Our study improved the Gff genome assembly with whole genome 10× Chromium sequencing of a lab reared pupae, identified autosomal versus sex-chromosomal regions of the genome with ddRA...

Lipid metabolism is critical for insect reproduction, especially for species that invest heavily in the early developmental stages of their offspring. The role of symbiotic bacteria during this process is understudied but likely essential. We examined the role of lipid metabolism during the interaction between the viviparous tsetse fly (Glossina mo...

Tsetse flies transmit trypanosomes-parasites that cause devastating diseases in humans and livestock-across much of sub-Saharan Africa. Chemical communication through volatile pheromones is common among insects; however, it remains unknown if and how such chemical communication occurs in tsetse flies. We identified methyl palmitoleate (MPO), methyl...

Tsetse flies ( Glossina spp.) feed exclusively on vertebrate blood. After a blood meal, the enteric endosymbiont Sodalis glossinidius is exposed to various environmental stressors including high levels of heme. To investigate how S . glossinidius morsitans ( Sgm ), the Sodalis subspecies that resides within the gut of G . morsitans ) tolerates the...

Tsetse flies ( Glossina spp.) feed exclusively on vertebrate blood. After a blood meal, the enteric endosymbiont Sodalis glossinidius is exposed to various environmental stressors including high levels of heme. To investigate how S. glossinidius morsitans (Sgm , the Sodalis subspecies that resides within the gut of G. morsitans ) tolerates the heme...

Tsetse flies ( Glossina spp.) house a population-dependent assortment of microorganisms that can include pathogenic African trypanosomes and maternally transmitted endosymbiotic bacteria, the latter of which mediate numerous aspects of their host’s metabolic, reproductive, and immune physiologies. One of these endosymbionts, Spiroplasma , was recen...

Tsetse flies are vectors of parasitic African trypanosomes, the etiological agents of human and animal African trypanosomoses. Current disease control methods include fly-repelling pesticides, fly trapping, and chemotherapeutic treatment of infected people and animals. Inhibiting tsetse’s ability to transmit trypanosomes by strengthening the fly’s...

Tsetse flies ( Glossina spp.) house a population-dependent assortment of microorganisms that can include pathogenic African trypanosomes and maternally transmitted endosymbiotic bacteria, the latter of which mediate numerous aspects of their host’s metabolic, reproductive, and immune physiologies. One of these endosymbionts, Spiroplasma , was recen...

Tsetse-transmitted African trypanosomes must develop into mammalian-infectious metacyclic cells in the fly's salivary glands (SGs) before transmission to a new host. The molecular mechanisms that underlie this developmental process, known as metacyclogen-esis, are poorly understood. Blocking the few metacyclic parasites deposited in saliva from fur...

Tsetse flies (Glossina spp.) have undergone evolutionary adaptations that facilitate their ability to feed solely on vertebrate blood and give birth to live young. These flies serve as cyclic vectors of pathogenic African trypanosomes, and as such, are of critical importance to human health and agricultural development in sub-Saharan Africa. This a...

Tsetse flies (Diptera: Glossinidae) house a taxonomically diverse microbiota that includes environmentally acquired bacteria, maternally transmitted symbiotic bacteria, and pathogenic African trypanosomes. Sodalis glossinidius, which is a facultative symbiont that resides intra and extracellularly within multiple tsetse tissues, has been implicated...

Background: Tsetse flies (Glossina sp.) are the vectors of human and animal trypanosomiasis throughout sub-Saharan Africa. Tsetse flies are distinguished from other Diptera by unique adaptations, including lactation and the birthing of live young (obligate viviparity), a vertebrate blood-specific diet by both sexes, and obligate bacterial symbiosi...

Tsetse flies (Glossina spp.) are vectors of parasitic trypanosomes, which cause human (HAT) and animal African trypanosomiasis (AAT) in sub-Saharan Africa. In Uganda, Glos-sina fuscipes fuscipes (Gff) is the main vector of HAT, where it transmits Gambiense disease in the northwest and Rhodesiense disease in central, southeast and western regions. E...

Tsetse flies (Glossina spp.) are vectors of parasitic trypanosomes, which cause human (HAT) and animal African trypanosomiasis (AAT) in sub-Saharan Africa. In Uganda, Glos-sina fuscipes fuscipes (Gff) is the main vector of HAT, where it transmits Gambiense disease in the northwest and Rhodesiense disease in central, southeast and western regions. E...

Parasites elicit several physiological changes in their host to enhance transmission. Little is known about the functional association between parasitism and microbiota-provisioned resources typically dedicated to animal hosts and how these goods may be rerouted to optimize parasite development. This study is the first to identify a specific symbio...

Tsetse flies (Diptera: Glossinidae) house a taxonomically diverse microbiota that includes environmentally acquired bacteria, maternally transmitted symbiotic bacteria, and pathogenic African trypanosomes. Sodalis glossinidius , which is a facultative symbiont that resides intra and extracellularly within multiple tsetse tissues, has been implicate...

[This corrects the article DOI: 10.1371/journal.ppat.1007470.].

Tsetse flies ( Glossina spp.) are vectors of parasitic trypanosomes, which cause human (HAT) and animal African trypanosomiasis (AAT) in sub-Saharan Africa. In Uganda, Glossina fuscipes fuscipes ( Gff ) is the main vector of HAT, where it transmits Gambiense disease in the northwest and Rhodesiense disease in central, southeast and western regions....

Dipteran or “true” flies occupy nearly every terrestrial habitat, and have evolved to feed upon a wide variety of sources including fruit, pollen, decomposing animal matter, and even vertebrate blood. Here we analyze the molecular, genetic and cellular basis of odor response in the tsetse fly Glossina morsitans, which feeds on the blood of humans a...

Fluorescent in situ hybridization of anti-sense and sense negative control RNA probes to cross sections of the G. morsitans antenna. All confocal images were taken with similar laser power and digital gain settings. (A, B) GmmObp59a, (C, D) GmmOrco, (E, F) GmmOr9, (G, H) GmmOr35, (I, J) GmmOr19, (K, L) GmmOr44. (TIF)

PCR primers used to amplify GmmOrs and GmmObps from cDNA. (XLSX)

Validation of CRISPR/Cas9 knock-in of the Gal4 transcription factor gene into the Or22a and Or22b coding regions. (A) Genomic region before and after it is targeted for CRISPR/Cas9-mediated homology-directed repair to knock in the Gal4 transcription factor and DsRed eye marker genes. The relative locations of PCR primers used for validating the ins...

Tsetse flies (Glossina spp.) vector pathogenic trypanosomes (Trypanosoma spp.) in sub-Saharan Africa. These parasites cause human and animal African trypanosomiases, which are debilitating diseases that inflict an enormous socio-economic burden on inhabitants of endemic regions. Current disease control strategies rely primarily on treating infected...

Background: Tsetse flies (Glossina sp.) are the sole vectors of human and animal trypanosomiasis throughout sub-Saharan Africa. Tsetse are distinguished from other Diptera by unique adaptations, including lactation and the birthing of live young (obligate viviparity), a vertebrate blood specific diet by both sexes and obligate bacterial symbiosis....

Background Symbiotic microbes represent a driving force of evolutionary innovation by conferring novel ecological traits to their hosts. Many insects are associated with microbial symbionts that contribute to their host’s nutrition, digestion, detoxification, reproduction, immune homeostasis, and defense. In addition, recent studies suggest a micro...

Background Tsetse flies (Diptera, Glossinidae) display unique reproductive biology traits. Females reproduce through adenotrophic viviparity, nourishing the growing larva into their modified uterus until parturition. Males transfer their sperm and seminal fluid, produced by both testes and male accessory glands, in a spermatophore capsule transient...

Background The tsetse fly (Glossina sp.) midgut is colonized by maternally transmitted and environmentally acquired bacteria. Additionally, the midgut serves as a niche in which pathogenic African trypanosomes reside within infected flies. Tsetse’s bacterial microbiota impacts many aspects of the fly’s physiology. However, little is known about the...

Abstract The tsetse fly (Glossina genus) is the main vector of African trypanosomes, which are protozoan parasites that cause human and animal African trypanosomiases in Sub-Saharan Africa. In the frame of the IAEA/FAO program ‘Enhancing Vector Refractoriness to Trypanosome Infection’, in addition to the tsetse, the cereal weevil Sitophilus has bee...

Tsetse flies ( Glossina spp.) vector pathogenic trypanosomes ( Trypanosoma spp.) in sub-Saharan Africa. These parasites cause human and animal African trypanosomiases, which are debilitating diseases that inflict an enormous socio-economic burden on inhabitants of endemic regions. Current disease control strategies rely primarily on treating infect...

With the absence of effective prophylactic vaccines and drugs against African trypanosomosis, control of this group of zoonotic neglected tropical diseases depends the control of the tsetse fly vector. When applied in an area-wide insect pest management approach, the sterile insect technique (SIT) is effective in eliminating single tsetse species f...

Background: The tsetse transmitted parasitic flagellate Trypanosoma congolense causes animal African trypanosomosis (AAT) across sub-Saharan Africa. AAT negatively impacts agricultural, economic, nutritional and subsequently, health status of the affected populace. The molecular mechanisms that underlie T. congolense's developmental program within...

Arthropod vectors have multiple physical and immunological barriers that impede the development and transmission of parasites to new vertebrate hosts. These barriers include the peritrophic matrix (PM), a chitinous barrier that separates the blood bolus from the midgut epithelia and thus modulates vector-microbiota interactions. In tsetse flies, a...

Ultrastructure of the cardia. (A) Transversal section of a non-infected cardia. Two pictures of the same cardia were merged to produce a larger picture. B, C, D, E and F are magnified micrographs of cardia tissues. (B) Midgut tissue delimiting the outer part of the cardia. (C) Foregut tissue invagination within cardia, corresponding to the stomodea...

Differentially expressed (DE) transcripts in parasitized cardia. (A) A total of 2,093 transcripts were DE in inf+/- and inf+/+ cardia relative to uninfected (non-inf) controls. In inf+/- cardia (red), 429 and 327 transcripts were up and downregulated, respectively. In inf+/+ cardia (blue), 278 and 413 transcripts were up and downregulated, respecti...

Detailed results and statistics for infection experiments and oxidative stress quantification. (XLSX)

GO terms analysis results. (XLSX)

Parasite quantity in midgut and cardia. (A) Number of parasites in the cardia of Inf+/- (red) and Inf+/+ (blue) flies. (B) Number of parasites in the midgut of Inf+/- (red) and Inf+/+ (blue) flies. The black bar represents the mean of the replicates for each treatment. Midgut and cardia were dissected from eight 40 days-old females. Parasites were...

Expression of chitin synthase after RNAi treatment. Expression of chitin synthase relative to constitutively expressed ß-tubulin after treatment with dsRNA-gfp (control; white circles) and dsRNA-chitin synthase (dsCS; gray circles). chitin synthase expression is significantly decreased after RNAi knockdown (Student t-test, p = 0.011). (TIF)

Overview of cardia transcriptomes. (A) Number of RNA-seq reads in each of three biological replicates from Non-inf, Inf +/- and Inf +/+ cardia. (B) Proportion of total trimmed reads that map to Glossina morsitans morsitans or Trypanosoma brucei brucei 927. (C) Percent relative abundance of mapped Glossina morsitans morsitans transcripts. (TIF)

Detailed results and analyses fo each transcriptome. (XLSX)

Ultrastructure of muscles and mitochondria in cardia from inf+/- tsetse. (A) Transversal section of muscle tissues (MU) composing the sphincter. (B-D) Longitudinal section of muscles (MU) layering the midgut tissues. Micrographs in this image represent three of five of biological replicates from cardia inf+/-. Black arrowheads: healthy mitochondria...

Arthropod vectors have multiple physical and immunological barriers that impede the development and transmission of parasites to new vertebrate hosts. These barriers include the peritrophic matrix (PM), a chitinous barrier that separates the blood bolus from the midgut epithelia and inturn, modulates vector-microbiota interactions. In tsetse flies,...

Vector-borne diseases are responsible for more than one million deaths every year but genomic resources for most species responsible for their transmission are limited. This is true for neglected diseases such as sleeping sickness (Human African Trypanosomiasis), a disease caused by Trypanosoma parasites vectored by several species of tseste flies...

Arthropod disease vectors and the bacterial microbes they carry exhibit varying levels of coevolutionary integration, and these associations reflect distinct host–microbe physiological codependences. The mosquito microbiota, which is largely transient and environmentally acquired during larval and adult stages, facilitates host maturation and modul...

Background Tsetse flies (Glossina spp.) are the prominent vector of African trypanosome parasites (Trypanosoma spp.) in sub-Saharan Africa, and Glossina pallidipes is the most widely distributed species in Kenya. This species displays strong resistance to infection by parasites, which are typically eliminated in the midgut shortly after acquisition...

Tsetse flies (Glossina spp.) transmit parasitic African trypanosomes (Trypanosoma spp.), including Trypanosoma congolense, which causes animal African trypanosomiasis (AAT). AAT detrimentally affects agricultural activities in sub-Saharan Africa and has negative impacts on the livelihood and nutrient availability for the affected communities. After...

Sheet 1. Genes with enriched expression in the proboscis (PB) compared to midgut [47] and whole head compared between uninfected PB and PB-infected with trypanosomes. The genes preferentially expressed in the PB (PB-enriched) was obtained by comparing expression of individual genes from tissues of uninfected flies. Sheet 2. Functional classificatio...

RNA-seq analysis comparing uninfected proboscis and those infected with trypanosomes from the complete transcriptome. (XLSX)

Immune-associated genes with differential expression based on RNA-seq analysis comparing uninfected PB and PB infected with trypanosomes. (XLSX)

An overview of G. m. morsitans proboscis RNA-transcriptome. (A) The total number of PB RNA-seq reads after quality control measures. (B) Proportion of reads that mapped per transcript. (C) Number of transcripts preferentially expressed in the PB (PB-enriched dataset) relative to the whole head and whole midgut transcriptomes. aPB-Proboscis—Trypanos...

Microscopic illustration of tsetse’s proboscis after Alexa Fluor 488 Phalloidin staining. (A, B and C) Tsetse’s labrum at its site of attachment to the thecal bulb, after removing the labium. The shape and general structure is observed by light microscopy, and muscles are fluorescence green after staining with phalloidin (dyes actin). Shown are the...

Graphical representation on transcript abundance of genes encoding mechanoreceptors. The heat map was generated by plotting the normalized RPKM values (Log2 transformed) of individual transcript from uninfected fly tissues, clustered using euclidean distance calculation and ward.D clustering methods. PB proboscis, WH whole head, WMG whole midgut, S...

Primers utilized for tsetse fly PB validation. (DOCX)

Genes encoding transmembrane and/or secreted proteins. (XLSX)

Validation of tsetse RNA-seq results with qPCR. (DOCX)

Insects with restricted diets rely on obligate microbes to fulfil nutritional requirements essential for biological function. Tsetse flies, vectors of African trypanosome parasites, feed exclusively on vertebrate blood and harbour the obligate endosymbiont Wigglesworthia glossinidia. Without Wigglesworthia, tsetse are unable to reproduce. These sym...

Figure S7: Differential metabolite abundances and enzyme associated gene expression in the pyrimidine metabolism pathway between control and aposymbiotic tsetse

Figure S6: Differential metabolite abundances and enzyme associated gene expression in the purine metabolism pathway between control and aposymbiotic tsetse

Table S2: Mapping Statistics of bacteriome RNA-Seq Reads to Wigglesworthia and Glossina Genomes

Table S6: Annotation and differential expression of Glossina genes with bacteriome enriched expression