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Polyamines in protozoan pathogens.

ABSTRACT: Polyamines are polycationic organic amines that are required for all eukaryotic life, exemplified by the polyamine spermidine, which plays an essential role in translation. They also play more specialized roles that differ across species, and their chemical versatility has been fully exploited during the evolution of protozoan pathogens. These eukaryotic pathogens, which cause some of the most globally widespread infectious diseases, have acquired species-specific polyamine-derived metabolites with essential cellular functions and have evolved unique mechanisms that regulate their core polyamine biosynthetic pathways. Many of these parasitic species have lost enzymes and or transporters from the polyamine metabolic pathway that are found in the human host. These pathway differences have prompted drug discovery efforts to target the parasite polyamine pathways, and indeed, the only clinically approved drug targeting the polyamine biosynthetic pathway is used to manage human African trypanosomiasis. This Minireview will primarily focus on polyamine metabolism and function in Trypanosoma, Leishmania, and Plasmodium species, which are the causative agents of human African trypanosomiasis (HAT) and Chagas disease, Leishmaniasis, and malaria, respectively. Aspects of polyamine metabolism across a diverse group of protozoan pathogens will also be explored.

SUBMITTER: Phillips MA

PROVIDER: S-EPMC6290135 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Polyamines in protozoan pathogens.

Phillips Margaret A MA

The Journal of biological chemistry 20181017 48

Polyamines are polycationic organic amines that are required for all eukaryotic life, exemplified by the polyamine spermidine, which plays an essential role in translation. They also play more specialized roles that differ across species, and their chemical versatility has been fully exploited during the evolution of protozoan pathogens. These eukaryotic pathogens, which cause some of the most globally widespread infectious diseases, have acquired species-specific polyamine-derived metabolites w ...[more]

PMID: 30333232

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Project description:Intestinal diseases caused by protistan parasites of the genera Giardia (giardiasis), Entamoeba (amoebiasis), Cryptosporidium (cryptosporidiosis) and Blastocystis (blastocystosis) represent a major burden in human and animal populations worldwide due to the severity of diarrhea and/or inflammation in susceptible hosts. These pathogens interact with epithelial cells, promoting increased paracellular permeability and enterocyte cell death (mainly apoptosis), which precede physiological and immunological disorders. Some cell-surface-anchored and molecules secreted from these parasites function as virulence markers, of which peptide hydrolases, particularly cysteine proteases (CPs), are abundant and have versatile lytic activities. Upon secretion, CPs can affect host tissues and immune responses beyond the site of parasite colonization, thereby increasing the pathogens' virulence. The four intestinal protists considered here are known to secrete predominantly clan A (C1- and C2-type) CPs, some of which have been characterized. CPs of Giardia duodenalis (e.g., Giardipain-1) and Entamoeba histolytica (EhCPs 1-6 and EhCP112) degrade mucin and villin, cause damage to intercellular junction proteins, induce apoptosis in epithelial cells and degrade immunoglobulins, cytokines and defensins. In Cryptosporidium, five Cryptopains are encoded in its genome, but only Cryptopains 4 and 5 are likely secreted. In Blastocystis sp., a legumain-activated CP, called Blastopain-1, and legumain itself have been detected in the extracellular medium, and the former has similar adverse effects on epithelial integrity and enterocyte survival. Due to their different functions, these enzymes could represent novel drug targets. Indeed, some promising results with CP inhibitors, such as vinyl sulfones (K11777 and WRR605), the garlic derivative, allicin, and purified amoebic CPs have been obtained in experimental models, suggesting that these enzymes might be useful drug targets.

Project description:Tick-borne diseases (TBDs) considerably impair equine health and productivity. Moreover, TBDs, particularly equine piroplasmosis, impede international movement and trade of equids, which is a vital component of the global horse racing industry. In the Philippines, horse racing is a lucrative industry generating millions of USD annually. However, information on equine TBDs is scarce. This study intended to describe molecularly the equine tick-borne infections in a racehorse park in Cavite, Philippines and identify the risk factors associated with the infections. One hundred twenty-four (n = 124) thoroughbred racehorses were sampled and screened for selected tick-borne protozoan and bacterial pathogens using polymerase chain reaction (PCR) assays. Racehorses were positive for Babesia caballi (12.10%; 15/124), Theileria equi (0.81%; 1/124), Anaplasma phagocytophilum (10.48%; 13/124), Borrelia burgdorferi sensu lato (38.71%; 48/124), A. marginale (0.81%; 1/124), and Coxiella burnetii (0.81%; 1/124). Rickettsia was not detected in the samples. Gender was determined as a significant risk factor for B. caballi infection. Sequencing analysis revealed that seven partial 18S rRNA B. caballi isolates shared 98.63-100% identity with each other and were classified as genotype A. Meanwhile, the sequence obtained from the lone T. equi-positive sample was 99.77% identical to isolates from Spain, Switzerland, China, Saudi Arabia, and South Korea, and was confirmed as genotype E based on the 18S rRNA gene. Eight Anaplasma 16S rRNA partial sequences were highly identical to A. phagocytophilum and A. ovis. Partial sequences of Borrelia 5-23S rRNA were most closely related to B. japonica and other Borrelia sp. isolates from various countries. This study reports the first molecular detection of Borrelia and Anaplasma and the identification of B. caballi and T. equi genotypes in racehorses in the Philippines. Findings from this study shall be useful in crafting equine tick and TBD control and prevention programs in the country.

Dataset Information

Polyamines in protozoan pathogens.

Publications

Polyamines in protozoan pathogens.

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