Trends in parasitology最新文献

Circumsporozoite protein-specific active and passive immunization can protect significantly against Plasmodium falciparum malaria and are being considered as tools to prevent placental malaria. Despite recent encouraging findings, a closer view of the underlying biology indicates significant challenges to preventing placental malaria.

The circumsporozoite protein (CSP) is one of the most studied proteins of the malaria parasite. It is the target of the only licensed malaria vaccines and is essential for sporozoite formation and infectivity. Yet, the mechanisms by which CSP functions and its interactions with other proteins are only beginning to be understood. Here we review the current state of knowledge of CSP structure and function, as sporozoites develop in the mosquito and establish infection in the mammalian host, and outline outstanding questions that need to be addressed.

Anthelmintic resistance (AR) in parasitic nematodes poses a global health problem in livestock and domestic animals and is an emerging problem in humans. Consequently, we must understand the mechanisms of AR, including target-site resistance (TSR), in which mutations affect drug binding, and non-target site resistance (NTSR), which involves alterations in drug metabolism and detoxification processes. Because much of the focus has been on TSR, NTSR has received less attention. Here, we describe how metabolomics approaches using Caenorhabditis elegans offer the ability to disentangle nematode drug metabolism, identify metabolic changes associated with resistance, uncover novel biomarkers, and enhance diagnostic methods.

Challenges in adapting natural products as antimalarials include their cryptic mechanism of action (and by extension resistance), as well as their complex and expensive synthesis without an abundant natural source. Recently, Chahine et al. presented plausible means to address these challenges in the case of the kalihinol family of isocyanoterpenes.

Congenital infections are a leading preventable cause of pregnancy complications impacting both mother and fetus. Although advancements have been made in understanding various congenital infections, the mechanisms of parasitic infections during pregnancy remain poorly understood. This review covers the global incidence of three parasites capable of congenital transmission - Trypanosoma cruzi, Plasmodium spp., and Toxoplasma gondii - and the state of research into their transplacental transmission strategies. We highlight technological advancements in placental modeling that offer opportunities to reveal how parasites cause gestational pathology. Additionally, we discuss the likelihood that selective adaptation contributed to the evolution of mechanisms that facilitate placental infection. These insights provide a foundation for understanding the progression and pathology of congenital parasitic diseases and identifying future research directions.

Many apicomplexan parasites have a chloroplast-derived apicoplast containing several metabolic pathways. Recent studies have greatly expanded our understanding of apicoplast biogenesis and metabolism while also raising new questions. Here, we review recent progress on the biological roles of individual metabolic pathways, focusing on two medically important parasites, Plasmodium spp. and Toxoplasma gondii. We highlight the similarities and differences in how similar apicoplast metabolic pathways are utilized to adapt to different parasitic lifestyles. The execution of apicoplast metabolic functions requires extensive interactions with other subcellular compartments, but the underlying mechanisms remain largely unknown. Apicoplast metabolic functions have historically been considered attractive drug targets, and a comprehensive understanding of their metabolic capacities and interactions with other organelles is essential to fully realize their potential.

Cadena et al. recently discovered a conserved trypanosomatid 'nabelschnur' protein TbNAB70 from a search through the protein localization resource TrypTag, providing new insight into kinetoplast origin and evolution.

Regulation of intracellular cyclic nucleotides to avoid homeostatic imbalances is achieved through catabolic activity of phosphodiesterases (PDEs). Recently, Ajiboye et al. reported validation of Cryptosporidium PDE1 (CpPDE1) as a viable drug target and identified optimized pyrazolopyrimidines with selective activity against CpPDE1 over human PDEs and with potent anticryptosporidial efficacy.

Plasmodium spp. have an ancient history with humans, having been described in ancient texts dating back 3500 years ago, which has led to an evolutionary arms race between Plasmodium and humans with Plasmodium successfully subverting durable, sterilizing host immunity. Mechanisms of immune evasion include polymorphism and antigenic variation, as well as dysregulated immune responses, each facilitating transmission and Plasmodium parasite persistence. Notably, metabolite signaling cues in the host and parasite have more recently been appreciated as key drivers for disease progression. Here, we highlight the metabolic interplay between the host and Plasmodium parasites during malaria. We discuss how immunometabolism studies may be leveraged to elucidate this complex relationship and offer opportunities to augment either vaccine- or infection-induced protective immunity.