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Lab evolution, transcriptomics, and modeling reveal mechanisms of paraquat tolerance

ABSTRACT: Lab evolution, transcriptomics, and modeling reveal mechanisms of paraquat tolerance

PROVIDER: PRJNA913892 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR22811703_1.fastq.gz	Fastqsanger.gz
	SRR22811703_2.fastq.gz	Fastqsanger.gz
	SRR22811704_1.fastq.gz	Fastqsanger.gz
	SRR22811704_2.fastq.gz	Fastqsanger.gz
	SRR22811705_1.fastq.gz	Fastqsanger.gz

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Project description:A deeper understanding of malaria parasite development inside the Anopheles mosquito may lead to the identification of processes that can be targeted by transmission-blocking interventions. Paraquat (1,1'-dimethyl-4,4'-bipyridylium dichloride) is a potent superoxide-inducing agent that impacts Plasmodium ookinete development, especially at higher concentrations. Compounds like Paraquat can potentially induce an oxidative imbalance in the mosquito midgut during ookinete maturation, essentially super-stressing the parasite leading to the arrested development of ookinetes, the only stage that can invade through a mosquito midgut cell to establish an oocyst infection in the mosquito. The mosquito midgut has evolved to handle the natural production of reactive oxygen and nitrogen species (ROS and RNS, respectively) as a result of feeding on blood. The addition of Paraquat to a bloodmeal is expected to induce a cognate response in the midgut to handle the excess ROS/RNS, and high concentrations of this compound can potentially overwhelm the midgut response leading to mosquito death. While several studies have explored the effect of Paraquat on malaria parasites, a fundamental understanding of the mosquito response to this compound remains unknown. Here, we quantified the mosquito midgut proteomic response to a Paraquat-laced sugar meal to understand the intrinsic midgut response (in the absence of a bloodmeal). We then carried out transcriptomic analysis of the mosquito midgut for several antioxidants of the Trx and GSH pathways to compare concordance or discordance between protein and its transcripts during different oxidative stress conditions. Finally, we determined whether the same Trx and GSH pathways are upregulated following infection with either P. falciparum or P. berghei at 24 hrs post-blood feeding, coinciding with the time point for maximal ookinete traversal of the midgut. We discuss the potential selective action of Paraquat on the parasite and the intrinsic tolerance of the mosquito midgut to Paraquat-mediated oxidative stress.

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Lab evolution, transcriptomics, and modeling reveal mechanisms of paraquat tolerance

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