title: Metarhizium anisopliae pathogenesis of mosquito larvae: a verdict of accidental death.
abstract: Metarhizium anisopliae, a fungal pathogen of terrestrial arthropods, kills the aquatic larvae of Aedes aegypti, the vector of dengue and yellow fever. The fungus kills without adhering to the host cuticle. Ingested conidia also fail to germinate and are expelled in fecal pellets. This study investigates the mechanism by which this fungus adapted to terrestrial hosts kills aquatic mosquito larvae. Genes associated with the M. anisopliae early pathogenic response (proteinases Pr1 and Pr2, and adhesins, Mad1 and Mad2) are upregulated in the presence of larvae, but the established infection process observed in terrestrial hosts does not progress and insecticidal destruxins were not detected. Protease inhibitors reduce larval mortality indicating the importance of proteases in the host interaction. The Ae. aegypti immune response to M. anisopliae appears limited, whilst the oxidative stress response gene encoding for thiol peroxidase is upregulated. Cecropin and Hsp70 genes are downregulated as larval death occurs, and insect mortality appears to be linked to autolysis through caspase activity regulated by Hsp70 and inhibited, in infected larvae, by protease inhibitors. Evidence is presented that a traditional host-pathogen response does not occur as the species have not evolved to interact. M. anisopliae retains pre-formed pathogenic determinants which mediate host mortality, but unlike true aquatic fungal pathogens, does not recognise and colonise the larval host.
authors.affiliation: College of Science, Swansea University, Swansea, United Kingdom.
authors.forename: Tariq M
authors.initials: TM
authors.lastname: Butt
authors.affiliation: College of Science, Swansea University, Swansea, United Kingdom.
authors.forename: Bethany P J
authors.initials: BP
authors.lastname: Greenfield
authors.affiliation: College of Science, Swansea University, Swansea, United Kingdom.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Greig
authors.affiliation: College of Engineering, Swansea University, Swansea, United Kingdom.
authors.forename: Thierry G G
authors.initials: TG
authors.lastname: Maffeis
authors.affiliation: College of Science, Swansea University, Swansea, United Kingdom.
authors.forename: James W D
authors.initials: JW
authors.lastname: Taylor
authors.affiliation: College of Science, Swansea University, Swansea, United Kingdom.
authors.forename: Justyna
authors.initials: J
authors.lastname: Piasecka
authors.affiliation: College of Medicine, Swansea University, Swansea, United Kingdom.
authors.forename: Ed
authors.initials: E
authors.lastname: Dudley
authors.affiliation: College of Science, Swansea University, Swansea, United Kingdom.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Abdulla
authors.affiliation: Institute of Systematics and Ecology of Animals, Siberian Branch of Russian Academy of Sciences, Novosibirsk, Russia.
authors.forename: Ivan M
authors.initials: IM
authors.lastname: Dubovskiy
authors.affiliation: Department of Agricultural and Forestry Sciences, University of Cordoba, Cordoba, Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Garrido-Jurado
authors.affiliation: Department of Agricultural and Forestry Sciences, University of Cordoba, Cordoba, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Quesada-Moraga
authors.affiliation: College of Engineering, Swansea University, Swansea, United Kingdom.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Penny
authors.affiliation: College of Science, Swansea University, Swansea, United Kingdom.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Eastwood
mesh_terms: D000330:Aedes / Q000235:genetics / Q000382:microbiology*; D000818:Animals; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D054807:Cecropins / Q000235:genetics / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D054884:Host-Pathogen Interactions; D019476:Insect Proteins / Q000235:genetics* / Q000378:metabolism; D007814:Larva / Q000235:genetics / Q000382:microbiology*; D052981:Metarhizium / Q000235:genetics / Q000472:pathogenicity*; D010544:Peroxidases / Q000235:genetics / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism; D013172:Spores, Fungal / Q000235:genetics / Q000472:pathogenicity*; D014774:Virulence
chemical_list: D054807:Cecropins; D005656:Fungal Proteins; D018840:HSP70 Heat-Shock Proteins; D019476:Insect Proteins; D011480:Protease Inhibitors; D010544:Peroxidases; D012697:Serine Endopeptidases; C093192:pr1 protein, Metarhizium anisopliae; D020169:Caspases