scholarly journals Intestinal delta-6-desaturase activity determines host range for Toxoplasma sexual reproduction

2019 ◽  
Author(s):  
Bruno Martorelli Di Genova ◽  
Sarah K. Wilson ◽  
J.P. Dubey ◽  
Laura J. Knoll

AbstractMany eukaryotic microbes have complex lifecycles that include both sexual and asexual phases with strict species-specificity. While the asexual cycle of the protistan parasite Toxoplasma gondii can occur in any warm-blooded mammal, the sexual cycle is restricted to the feline intestine1. The molecular determinants that identify cats as the definitive host for T. gondii are unknown. Here, we defined the mechanism of species specificity for T. gondii sexual development and break the species barrier to allow the sexual cycle to occur in mice. We determined that T. gondii sexual development occurs when cultured feline intestinal epithelial cells are supplemented with linoleic acid. Felines are the only mammals that lack delta-6-desaturase activity in their intestines, which is required for linoleic acid metabolism, resulting in systemic excess of linoleic acid2, 3. We found that inhibition of murine delta-6-desaturase and supplementation of their diet with linoleic acid allowed T. gondii sexual development in mice. This mechanism of species specificity is the first defined for a parasite sexual cycle. This work highlights how host diet and metabolism shape coevolution with microbes. The key to unlocking the species boundaries for other eukaryotic microbes may also rely on the lipid composition of their environments as we see increasing evidence for the importance of host lipid metabolism during parasitic lifecycles4, 5. Pregnant women are advised against handling cat litter as maternal infection with T. gondii can be transmitted to the fetus with potentially lethal outcomes. Knowing the molecular components that create a conducive environment for T. gondii sexual reproduction will allow for development of therapeutics that prevent shedding of T. gondii parasites. Finally, given the current reliance on companion animals to study T. gondii sexual development, this work will allow the T. gondii field to use of alternative models in future studies.


PLoS Biology ◽  
2019 ◽  
Vol 17 (8) ◽  
pp. e3000364 ◽  
Author(s):  
Bruno Martorelli Di Genova ◽  
Sarah K. Wilson ◽  
J. P. Dubey ◽  
Laura J. Knoll


Author(s):  
Andi M. Wilson ◽  
P. Markus Wilken ◽  
Michael J. Wingfield ◽  
Brenda D. Wingfield

Sexual development in filamentous fungi is a complex process that relies on the precise control of and interaction between a variety of genetic networks and pathways. The mating-type ( MAT ) genes are the master regulators of this process and typically act as transcription factors, which control the expression of genes involved all stages of the sexual cycle.



2013 ◽  
Vol 12 (12) ◽  
pp. 1629-1640 ◽  
Author(s):  
Riyad N. H. Seervai ◽  
Stephen K. Jones ◽  
Matthew P. Hirakawa ◽  
Allison M. Porman ◽  
Richard J. Bennett

ABSTRACTCandidaspecies exhibit a variety of ploidy states and modes of sexual reproduction. Most species possess the requisite genes for sexual reproduction, recombination, and meiosis, yet only a few have been reported to undergo a complete sexual cycle including mating and sporulation.Candida albicans, the most studiedCandidaspecies and a prevalent human fungal pathogen, completes its sexual cycle via a parasexual process of concerted chromosome loss rather than a conventional meiosis. In this study, we examine ploidy changes inCandida tropicalis, a closely related species toC. albicansthat was recently revealed to undergo sexual mating.C. tropicalisdiploid cells mate to form tetraploid cells, and we show that these can be induced to undergo chromosome loss to regenerate diploid forms by growth on sorbose medium. The diploid products are themselves mating competent, thereby establishing a parasexual cycle in this species for the first time. Extended incubation (>120 generations) ofC. tropicalistetraploid cells under rich culture conditions also resulted in instability of the tetraploid form and a gradual reduction in ploidy back to the diploid state. The fitness levels ofC. tropicalisdiploid and tetraploid cells were compared, and diploid cells exhibited increased fitness relative to tetraploid cellsin vitro, despite diploid and tetraploid cells having similar doubling times. Collectively, these experiments demonstrate distinct pathways by which a parasexual cycle can occur inC. tropicalisand indicate that nonmeiotic mechanisms drive ploidy changes in this prevalent human pathogen.



1986 ◽  
Vol 32 (2) ◽  
pp. 79-82 ◽  
Author(s):  
Keith E. Lewis ◽  
Danton H. O'Day

During the sexual cycle of Dictyostelium discoideum, zygote giant cells develop and serve as foci for further development by chemoattracting and cannibalizing hundreds of local amoebae. Previous work has shown that the phagocytic process bears similarities to and differences from asexual endocytosis. In the present study, sexual phagocytosis in D. discoideum was found to be species and developmental stage specific. It was inhibited selectively by glucose and concanavalin A. Although a partial, inhibitory effect of mannose on phagocytosis was not statistically significant, alpha-methylmannosamine, like alpha-methyl-glucose, significantly restored the phagocytic competence of giant cells treated with concanavalin A. Other sugars (N-acetyl glucosamine, N-acetylgalactosamine, and galactose) and lectins (wheat germ agglutinin, Ulex europus type I, and Ricinis communis agglutinin type I) had no significant effect on sexual phagocytosis. Together these data indicate that a glucose-type receptor is involved in selective uptake of D. discoideum amoebae by giant cells.



1988 ◽  
Vol 90 (2) ◽  
pp. 287-293
Author(s):  
M. F. CHAU ◽  
STEPHEN F. NG

The present study further analyses the importance of postmeiotic divisional derivatives of the micronucleus in the development of the oral apparatus of Paramecium during sexual reproduction. Cell lines possessing defective micronuclei generated by laser microbeam irradiation of the micronucleus were employed. They exhibited anomalies in nuclear reorganization and stomatogenesis in the sexual cycle. During autogamy, in some cells the micronuclear cycle terminated shortly after meiosis, resulting in the loss of all postmeiotic micronuclear derivatives. Stomatogenesis became arrested at an early stage of assembly of the oral membranelles, but the old oral apparatus was resorbed as usual, leading to the production of astomatous cells at the end of the sexual cycle. Conjugation of these cell lines with normal micronucleates rescued both nucleogenesis and stomatogenesis in the defective micronucleate conjugant, primarily as a result of transfer of the male gametic nucleus from the normal conjugant to the defective-micronucleate mate. These observations demonstrate the stomatogenic significance, in particular in the initiation of oral membranelle assembly, of the gametic nuclei during sexual reproduction. The present study also suggests the possibility of micronuclear activities in the early part of the sexual cycle affecting postzygotic nucleogenesis.



mBio ◽  
2019 ◽  
Vol 10 (2) ◽  
Author(s):  
Zheng Wang ◽  
Cristina Miguel-Rojas ◽  
Francesc Lopez-Giraldez ◽  
Oded Yarden ◽  
Frances Trail ◽  
...  

ABSTRACTFungal spores germinate and undergo vegetative growth, leading to either asexual or sexual reproductive dispersal. Previous research has indicated that among developmental regulatory genes, expression is conserved across nutritional environments, whereas pathways for carbon and nitrogen metabolism appear highly responsive—perhaps to accommodate differential nutritive processing. To comprehensively investigate conidial germination and the adaptive life history decision-making underlying these two modes of reproduction, we profiled transcription ofNeurospora crassagerminating on two media: synthetic Bird medium, designed to promote asexual reproduction; and a natural maple sap medium, on which both asexual reproduction and sexual reproduction manifest. A later start to germination but faster development was observed on synthetic medium. Metabolic genes exhibited altered expression in response to nutrients—at least 34% of the genes in the genome were significantly downregulated during the first two stages of conidial germination on synthetic medium. Knockouts of genes exhibiting differential expression across development altered germination and growth rates, as well as in one case causing abnormal germination. A consensus Bayesian network of these genes indicated especially tight integration of environmental sensing, asexual and sexual development, and nitrogen metabolism on a natural medium, suggesting that in natural environments, a more dynamic and tentative balance of asexual and sexual development may be typical ofN. crassacolonies.IMPORTANCEOne of the most remarkable successes of life is its ability to flourish in response to temporally and spatially varying environments. Fungi occupy diverse ecosystems, and their sensitivity to these environmental changes often drives major fungal life history decisions, including the major switch from vegetative growth to asexual or sexual reproduction. Spore germination comprises the first and simplest stage of vegetative growth. We examined the dependence of this early life history on the nutritional environment using genome-wide transcriptomics. We demonstrated that for developmental regulatory genes, expression was generally conserved across nutritional environments, whereas metabolic gene expression was highly labile. The level of activation of developmental genes did depend on current nutrient conditions, as did the modularity of metabolic and developmental response network interactions. This knowledge is critical to the development of future technologies that could manipulate fungal growth for medical, agricultural, or industrial purposes.



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