Abstract
The big data movement has led to major advances in our ability to assess vast and complex datasets related to the host and parasite during malaria infection. While host and parasite genomics and transcriptomics are often the focus of many computational efforts in malaria research, metabolomics represents another big data type that has great promise for aiding our understanding of complex host-parasite interactions that lead to the transmission of malaria. Recent analyses of the complement of metabolites present in human blood, skin and breath suggest that host metabolites play a critical role in the transmission cycle of malaria. Volatile compounds released through breath and skin serve as attractants to mosquitoes, with malaria-infected hosts appearing to have unique profiles that further increase host attractiveness. Inside the host, fluctuations in the levels of certain metabolites in blood may trigger increased production of transmission-competent sexual stages (gametocytes), setting the stage for enhanced transmission of malaria from human to mosquito. Together, these recent discoveries suggest that metabolites of human blood, skin and breath play critical roles in malaria transmission. This review discusses recent advances in this area, with a focus on metabolites that have been identified to play a role in malaria transmission and methods that may lead to an improved understanding of malaria transmission.
Highlights
INTRODUCTIONTechnological advancements have been made in recent years in sequencing-based (genomics, transcriptomics, epigenomics) and mass spectrometry-based approaches (proteomics, lipidomics, and metabolomics)
Technological advancements have been made in recent years in sequencing-based and mass spectrometry-based approaches
In addition to Plasmodium’s ability to replicate asexually within the blood cells of vertebrate hosts, Plasmodium undergoes complex stage conversions to successfully transmit itself to the invertebrate host (Anopheles mosquito), where it must again undergo a series of stage conversions to be successfully delivered to the vertebrate host
Summary
Technological advancements have been made in recent years in sequencing-based (genomics, transcriptomics, epigenomics) and mass spectrometry-based approaches (proteomics, lipidomics, and metabolomics). The following sections focus on how metabolites in the blood, skin and breath of malaria-infected hosts play key roles in malaria transmission through modulating (a) the attractiveness of hosts to mosquitoes and (b) the rate of gametocyte development within host blood It has been known for some time that carbon dioxide (CO2) and other volatile chemicals help mosquitoes locate their vertebrate hosts and that certain molecules released through the skin, sweat and/or breath of vertebrates are attractive to mosquitoes (Brouwer, 1960; Takken and Kline, 1989). In a further effort to identify VOCs derived from malaria parasites, an analysis of headspace from in vitro Plasmodium cultures was performed, and the headspace of the extracellular vesicles (EV) fraction revealed an enrichment of a previously reported mosquito attractant aldehyde, hexanal (Correa et al, 2017) (Table 1) Taking this concept a step further, a subset of studies have combined HS-GCMS with functional sensory tests in order to identify specific components of the metabolome that are detected by a mosquito’s antenna.
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