A natural Anopheles-associated Penicillium chrysogenum enhances mosquito susceptibility to Plasmodium infection

Abstract

Whereas studies have extensively examined the ability of bacteria to influence Plasmodium infection in the mosquito, the tripartite interactions between non-entomopathogenic fungi, mosquitoes, and Plasmodium parasites remain largely uncharacterized. Here we report the isolation of a common mosquito-associated ascomycete fungus, Penicillium chrysogenum, from the midgut of field-caught Anopheles mosquitoes. Although the presence of Pe. chrysogenum in the Anopheles gambiae midgut does not affect mosquito survival, it renders the mosquito significantly more susceptible to Plasmodium infection through a secreted heat-stable factor. We further provide evidence that the mechanism of the fungus-mediated modulation of mosquito susceptibility to Plasmodium involves an upregulation of the insect’s ornithine decarboxylase gene, which sequesters arginine for polyamine biosynthesis. Arginine plays an important role in the mosquito’s anti-Plasmodium defense as a substrate of nitric oxide production, and its availability therefore has a direct impact on the mosquito’s susceptibility to the parasite. While this type of immunomodulatory mechanism has already been demonstrated in other host-pathogen interaction systems, this is the first report of a mosquito-associated fungus that can suppress the mosquito’s innate immune system in a way that would favor Plasmodium infection and possibly malaria transmission.

Disruption of mosGILT in Anopheles gambiae impairs ovarian development and Plasmodium infection

“…A. gambiae mosquitoes were starved for 3-5 h and then fed on NF54 P. falciparum gametocyte cultures (NF54: BEI Resources, MRA-1000; mature gametocytes were adjusted to 0.02% in 40% human red blood cells [O + ] containing 60% heat-inactivated human serum [O + ]; please refer to the ethics statement) through artificial membranes at 37°C at the Johns Hopkins Malaria Institute Core Facility as previously described (Angleró-Rodríguez et al, 2016;Dong et al, 2018;Trager and Jensen, 1976). Unfed mosquitoes were removed immediately after blood feeding, and the remaining mosquitoes were incubated at 27°C for 8 d to check oocysts in the midgut, or 14 d to check sporozoites in the SGs.…”

Effects of fungal infection on the survival of parasitic bat flies

“…As bat flies are vectors of bat malaria-like parasites, Laboulbeniales infection might affect vectorial capacity. For instance, in mosquitoes, Penicillium infection has been observed to increase susceptibility to Plasmodium infection [67] which in turn can reduce the survival of the vector [68]. In addition, the presence of Polychromophilus infection is known to reduce bat fly lifespan [36], although not investigated in this study, it might also have additional interaction with Laboulbeniales infection.…”

An Aedes aegypti-associated fungus increases susceptibility to dengue virus by modulating gut trypsin activity

“…Feeding mosquitoes on whole P. chrysogenum conidia, or culture filtrates, did not affect DENV infection (p=0.829, p=0.867, respectively) ( Figure 4A,B , Figure 4—source data 1 ). We have previously associated P. chrysogenum with an enhancement of Plasmodium infection in Anopheles gambiae ( Angleró-Rodríguez et al, 2016 ). To test whether Tsp_PR could influence malaria parasite infection in its vector we provided Tsp_PR to An.…”

“…However, modulation of infection does not seem to be a general property of a closely related Penicillium species, since exposure of Ae. aegypti to whole spores or the secretome of another mosquito-associated species, Penicillium chrysogenum, did not affect DENV infection ( Angleró-Rodríguez et al, 2016 ). Our study suggests that Tsp_PR produces a factor(s) that is a likely a heat-sensitive protein or metabolite that alters the mosquito’s susceptibility to DENV.…”

“…Studies have shown that some bacterial species can inhibit DENV infection and other human pathogens ( Bahia et al, 2014 ; Dennison et al, 2014 ; Ramirez et al, 2012 , 2014 ). However, the midgut microbiota also comprises fungi, but little is yet known about the mosquito’s mycobiome ( Angleró-Rodríguez et al, 2016 ; da Costa and de Oliveira, 1998 ; da S Pereira et al, 2009 ). Most studies have focused on entomopathogenic fungi for use in mosquito control ( Dong et al, 2012 ; Scholte et al, 2007 ).…”