title: Analysis of the metabolome of Anopheles gambiae mosquito after exposure to Mycobacterium ulcerans.
abstract: Infection with Mycobacterium ulcerans causes Buruli Ulcer, a neglected tropical disease. Mosquito vectors are suspected to participate in the transmission and environmental maintenance of the bacterium. However, mechanisms and consequences of mosquito contamination by M. ulcerans are not well understood. We evaluated the metabolome of the Anopheles gambiae mosquito to profile the metabolic changes associated with bacterial colonization. Contamination of mosquitoes with live M. ulcerans bacilli results in disruptions to lipid metabolic pathways of the mosquito, specifically the utilization of glycerolipid molecules, an affect that was not observed in mosquitoes exposed to dead M. ulcerans. These results are consistent with aberrations of lipid metabolism described in other mycobacterial infections, implying global host-pathogen interactions shared across diverse saprophytic and pathogenic mycobacterial species. This study implicates features of the bacterium, such as the putative M. ulcerans encoded phospholipase enzyme, which promote virulence, survival, and active adaptation in concert with mosquito development, and provides significant groundwork for enhanced studies of the vector-pathogen interactions using metabolomics profiling. Lastly, metabolic and survival data suggest an interaction which is unlikely to contribute to transmission of M. ulcerans by A. gambiae and more likely to contribute to persistence of M. ulcerans in waters cohabitated by both organisms.
authors.affiliation: Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523.
authors.forename: J Charles
authors.initials: JC
authors.lastname: Hoxmeier
authors.affiliation: Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523.
authors.forename: Brice D
authors.initials: BD
authors.lastname: Thompson
authors.affiliation: Proteomics and Metabolomics Facility, Colorado State University, Fort Collins, CO 80523.
authors.forename: Corey D
authors.initials: CD
authors.lastname: Broeckling
authors.affiliation: Department of Microbiology, University of Tennessee at Knoxville, Knoxville, TN 37996.
authors.forename: Pamela
authors.initials: P
authors.lastname: Small
authors.affiliation: Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Foy
authors.affiliation: 1] Proteomics and Metabolomics Facility, Colorado State University, Fort Collins, CO 80523 [2] Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO 80523.
authors.forename: Jessica
authors.initials: J
authors.lastname: Prenni
authors.affiliation: Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523.
authors.forename: Karen M
authors.initials: KM
authors.lastname: Dobos
mesh_terms: D000818:Animals; D000852:Anopheles / Q000378:metabolism* / Q000382:microbiology; D016000:Cluster Analysis; D005227:Fatty Acids / Q000378:metabolism; D013058:Mass Spectrometry; D055442:Metabolome; D019911:Mycobacterium ulcerans / Q000472:pathogenicity*; D010743:Phospholipids / Q000378:metabolism; D025341:Principal Component Analysis
chemical_list: D005227:Fatty Acids; D010743:Phospholipids