Plasmodium berghei

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Plasmodium berghei
Berghei 01.png
Blood-borne forms
Scientific classification OOjs UI icon edit-ltr.svg
Domain: Eukaryota
Clade: Diaphoretickes
Clade: SAR
Clade: Alveolata
Phylum: Apicomplexa
Class: Aconoidasida
Order: Haemospororida
Family: Plasmodiidae
Genus: Plasmodium
Species:
P. berghei
Binomial name
Plasmodium berghei
Vincke & Lips, 1948
Strains

Plasmodium berghei is a single-celled parasite causing rodent malaria. It is in the Plasmodium subgenus Vinckeia .

Contents

Originally, isolated from thicket rats in Central Africa, P. berghei is one of four Plasmodium species that have been described in African murine rodents, the others being P. chabaudi , P. vinckei , and P. yoelii . Due to its ability to infect rodents and relative ease of genetic engineering, P. berghei is a popular model organism for the study of human malaria.

Biology

Like all malaria parasites of mammals, including the four human malaria parasites, P. berghei is transmitted by Anopheles mosquitoes and it infects the liver after being injected into the bloodstream by a bite of an infected female mosquito. After a short period (a few days) of development and multiplication, these parasites leave the liver and invade erythrocytes (red blood cells). The multiplication of the parasite in the blood causes the pathology such as anaemia and damage of essential organs of the host such as lungs, liver, spleen. P. berghei infections may also affect the brain and can be the cause of cerebral complications in laboratory mice (cerebral murine malaria, CMM). These symptoms are to a certain degree comparable to symptoms of cerebral malaria in patients infected with the human malaria parasite Plasmodium falciparum . [3]

Although sexuality is necessary in vivo in P. berghei as normal for most sexual organisms, it is a stark competitive disadvantage in vitro. Sinha et al., 2014 implement both mechanical passaging and competitive assay to demonstrate the advantage of loss of gametocyte production: During mechanical passage successive generations are found to naturally trend toward lower gametocytaemia; and nonsexuals outcompete sexuals rapidly when placed together in vitro. [4] :575

Immunochemistry

Endothelin 1 has an uncertain role in producing cerebral murine malaria. [2] Martins et al., 2016 find blockade of endothelin-1 prevents CMM and its symptoms and supplementation helps to produce it. [2] Subramaniam et al., 2015 find mice increase production of BTNL2 during infection and so it is probably protective. [2] Chertow et al., 2015 find the asymmetric dimethylarginine-to-arginine ratio is indicative of disease severity in mice with P. berghei ANKA. [5] [6] This ratio is a metric of arginine bioavailability and in this disease they find it predicts degree of endothelial dysfunction. [5] [6]

Strains

Some strains produce cerebral murine malaria and some do not. [2]

See section above for specific molecules' interactions.

Distribution

Plasmodium berghei is found in the forests of Central Africa, where its natural cyclic hosts are the thicket rat ( Grammomys surdaster ) and the mosquito ( Anopheles dureni ).

Hosts

Plasmodium berghei was first identified in the thicket rat ( Grammomys surdaster ). It has also been described in Leggada bella , Praomys jacksoni and Thamnomys surdaster.[ citation needed ] In research laboratories, various rodents can be infected, such as mice ( Mus musculus ), rats and gerbils ( Meriones unguiculatus ). [7] In M. musculusP. b. ANKA, downregulation of responses is necessary to prevent self-inflicted damage leading to CMM. [8] [9] :97 Specifically, Sarfo et al., 2011 finds mice produce the cytokine interleukin-10 (cIL-10) to suppress otherwise-potentially-deadly CMM damage from others of their own immune factors. [8] [9]

The natural insect host of P. berghei is likely Anopheles dureni , however in laboratory conditions it has also been shown to infect An. stephensi .[ citation needed ]

Gene interactions

In Mus musculus ⇔ the P. b. ANKA strain various genes affect the incidence of cerebral murine malaria. Kassa et al., 2016 finds several genes to be of no effect:

They find one improves survival probability:

An. gambiae 's hemocytes transcribe a wide array of molecular responses to Plasmodium infections. [10] [11] :138 [12] [13] [14] [15] :221 In response to this species, Baton et al., 2009 find this includes increased expression of the prophenoloxidase gene, cascading to increase phenoloxidase and thereby melanization. [10] [11] :138 [12] [13] [14] [15] :221

Treatment

Some phytochemicals show efficacy against P. berghei. Bankole et al., 2016 find Markhamia tomentosa to be highly effective, comparable to chloroquine, while Monoon longifolium is also significantly effective. They find Trichilia heudelotii to be ineffective. [16]

History

This species was first described by Vincke and Lips in 1948 in the Belgian Congo. [17]

Live P. berghei expressing GFP (green) in erythrocytes; visualised using a fluorescence microscope Berghei 02.png
Live P. berghei expressing GFP (green) in erythrocytes; visualised using a fluorescence microscope
Infected mouse, with P. berghei in the lungs, spleen and adipose tissue. Transgenic parasites are visualized by their expression of the bioluminescent reporter protein Luciferase Berghei 03.png
Infected mouse, with P. berghei in the lungs, spleen and adipose tissue. Transgenic parasites are visualized by their expression of the bioluminescent reporter protein Luciferase
A liver cell with P. berghei (a schizont with daughter parasites) expressing mCherry (red). Here the parasite membrane is stained green with an antibody, while the nuclei of liver cells and parasites are stained with DAPI (blue) Liver stage malaria parasite.jpg
A liver cell with P. berghei (a schizont with daughter parasites) expressing mCherry (red). Here the parasite membrane is stained green with an antibody, while the nuclei of liver cells and parasites are stained with DAPI (blue)

Research

Plasmodium berghei infection of laboratory mouse strains is frequently used in research as a model for human malaria. [18] In the laboratory the natural hosts have been replaced by a number of commercially available laboratory mouse strains, and the mosquito Anopheles stephensi , which is comparatively easily reared and maintained under defined laboratory conditions.

P. berghei is used as a model organism for the investigation of human malaria because of its similarity to the Plasmodium species which cause human malaria. P. berghei has a very similar life-cycle to the species that infect humans, and it causes disease in mice which has signs similar to those seen in human malaria. Importantly, P. berghei can be genetically manipulated more easily than the species which infect humans, making it a useful model for research into Plasmodium genetics.

In several aspects the pathology caused by P. berghei in mice differs from malaria caused by P. falciparum in humans. In particular, while death from P. falciparum malaria in humans is most frequently caused by the accumulation of red blood cells in the blood vessels of the brain, it is unclear to what extent this occurs in mice infected with P. berghei. [18] Instead, in P. berghei infection, mice are found to have an accumulation of immune cells in brain blood vessels. [18] This has led some to question the use of P. berghei infections in mice as an appropriate model of cerebral malaria in humans. [18]

P. berghei can be genetically manipulated in the laboratory using standard genetic engineering technologies. Consequently, this parasite is often used for the analysis of the function of malaria genes using the technology of genetic modification. [19] [20] [21] Additionally, the genome of P. berghei has been sequenced and it shows a high similarity, both in structure and gene content, with the genome of the primate malaria parasite Plasmodium falciparum . [22] [23] [24]

A number of genetically modified P. berghei lines have been generated which express fluorescent reporter proteins such as Green Fluorescent Protein (GFP) and mCherry (red) or bioluminescent reporters such as Luciferase. These transgenic parasites are important tools to study and visualize the parasites in the living host. [25] [26]

P. berghei is used in research programs for development and screening of anti-malarial drugs and for the development of an effective vaccine against malaria. [27]

Related Research Articles

<span class="mw-page-title-main">Malaria</span> Mosquito-borne infectious disease

Malaria is a mosquito-borne infectious disease that affects humans and other vertebrates. Human malaria causes symptoms that typically include fever, fatigue, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or death. Symptoms usually begin 10 to 15 days after being bitten by an infected Anopheles mosquito. If not properly treated, people may have recurrences of the disease months later. In those who have recently survived an infection, reinfection usually causes milder symptoms. This partial resistance disappears over months to years if the person has no continuing exposure to malaria.

<i>Plasmodium</i> Genus of parasitic protists that can cause malaria

Plasmodium is a genus of unicellular eukaryotes that are obligate parasites of vertebrates and insects. The life cycles of Plasmodium species involve development in a blood-feeding insect host which then injects parasites into a vertebrate host during a blood meal. Parasites grow within a vertebrate body tissue before entering the bloodstream to infect red blood cells. The ensuing destruction of host red blood cells can result in malaria. During this infection, some parasites are picked up by a blood-feeding insect, continuing the life cycle.

<i>Anopheles</i> Genus of mosquito

Anopheles is a genus of mosquito first described by J. W. Meigen in 1818, and are known as nail mosquitoes and marsh mosquitoes. Many such mosquitoes are vectors of the parasite Plasmodium, a genus of protozoans that cause malaria in birds, reptiles, and mammals, including people. The Anopheles gambiae mosquito is the best-known species of marsh mosquito that transmits the Plasmodium falciparum, which is a malarial parasite deadly to human beings; no other mosquito genus is a vector of human malaria.

<i>Plasmodium falciparum</i> Protozoan species of malaria parasite

Plasmodium falciparum is a unicellular protozoan parasite of humans, and the deadliest species of Plasmodium that causes malaria in humans. The parasite is transmitted through the bite of a female Anopheles mosquito and causes the disease's most dangerous form, falciparum malaria. It is responsible for around 50% of all malaria cases. P. falciparum is therefore regarded as the deadliest parasite in humans. It is also associated with the development of blood cancer and is classified as a Group 2A (probable) carcinogen.

<span class="mw-page-title-main">Microsporidia</span> Phylum of fungi

Microsporidia are a group of spore-forming unicellular parasites. These spores contain an extrusion apparatus that has a coiled polar tube ending in an anchoring disc at the apical part of the spore. They were once considered protozoans or protists, but are now known to be fungi, or a sister group to fungi. These fungal microbes are obligate eukaryotic parasites that use a unique mechanism to infect host cells. They have recently been discovered in a 2017 Cornell study to infect Coleoptera on a large scale. So far, about 1500 of the probably more than one million species are named. Microsporidia are restricted to animal hosts, and all major groups of animals host microsporidia. Most infect insects, but they are also responsible for common diseases of crustaceans and fish. The named species of microsporidia usually infect one host species or a group of closely related taxa. Approximately 10 percent of the species are parasites of vertebrates —several species, most of which are opportunistic, can infect humans, in whom they can cause microsporidiosis.

<i>Plasmodium ovale</i> Species of single-celled organism

Plasmodium ovale is a species of parasitic protozoon that causes tertian malaria in humans. It is one of several species of Plasmodium parasites that infect humans, including Plasmodium falciparum and Plasmodium vivax which are responsible for most cases of malaria in the world. P. ovale is rare compared to these two parasites, and substantially less dangerous than P. falciparum.

<i>Plasmodium malariae</i> Species of single-celled organism

Plasmodium malariae is a parasitic protozoan that causes malaria in humans. It is one of several species of Plasmodium parasites that infect other organisms as pathogens, also including Plasmodium falciparum and Plasmodium vivax, responsible for most malarial infection. Found worldwide, it causes a so-called "benign malaria", not nearly as dangerous as that produced by P. falciparum or P. vivax. The signs include fevers that recur at approximately three-day intervals – a quartan fever or quartan malaria – longer than the two-day (tertian) intervals of the other malarial parasite.

<i>Plasmodium knowlesi</i> Species of single-celled organism

Plasmodium knowlesi is a parasite that causes malaria in humans and other primates. It is found throughout Southeast Asia, and is the most common cause of human malaria in Malaysia. Like other Plasmodium species, P. knowlesi has a life cycle that requires infection of both a mosquito and a warm-blooded host. While the natural warm-blooded hosts of P. knowlesi are likely various Old World monkeys, humans can be infected by P. knowlesi if they are fed upon by infected mosquitoes. P. knowlesi is a eukaryote in the phylum Apicomplexa, genus Plasmodium, and subgenus Plasmodium. It is most closely related to the human parasite Plasmodium vivax as well as other Plasmodium species that infect non-human primates.

Plasmodium chabaudi is a parasite of the genus Plasmodium subgenus Vinckeia. As in all Plasmodium species, P. chabaudi has both vertebrate and insect hosts. The vertebrate hosts for this parasite are rodents.

<i>Anopheles gambiae</i> Species of mosquito

The Anopheles gambiae complex consists of at least seven morphologically indistinguishable species of mosquitoes in the genus Anopheles. The complex was recognised in the 1960s and includes the most important vectors of malaria in sub-Saharan Africa, particularly of the most dangerous malaria parasite, Plasmodium falciparum. It is one of the most efficient malaria vectors known. The An. gambiae mosquito additionally transmits Wuchereria bancrofti which causes lymphatic filariasis, a symptom of which is elephantiasis.

Plasmodium yoelii is a parasite of the genus Plasmodium subgenus Vinckeia. As in all Plasmodium species, P. yoelii has both vertebrate and insect hosts. The vertebrate hosts for this parasite are mammals.

Vinckeia is a subgenus of the genus Plasmodium — all of which are parasitic alveolates. The subgenus Vinckeia was created by Cyril Garnham in 1964 to accommodate the mammalian parasites other than those infecting the primates.

Malaria vaccines are vaccines that prevent malaria, a mosquito-borne infectious disease which annually affects an estimated 247 million people worldwide and causes 619,000 deaths. The first approved vaccine for malaria is RTS,S, known by the brand name Mosquirix. As of April 2023, the vaccine has been given to 1.5 million children living in areas with moderate-to-high malaria transmission. It requires at least three doses in infants by age 2, and a fourth dose extends the protection for another 1–2 years. The vaccine reduces hospital admissions from severe malaria by around 30%.

<span class="mw-page-title-main">Avian malaria</span> Parasitic disease of birds

Avian malaria is a parasitic disease of birds, caused by parasite species belonging to the genera Plasmodium and Hemoproteus. The disease is transmitted by a dipteran vector including mosquitoes in the case of Plasmodium parasites and biting midges for Hemoproteus. The range of symptoms and effects of the parasite on its bird hosts is very wide, from asymptomatic cases to drastic population declines due to the disease, as is the case of the Hawaiian honeycreepers. The diversity of parasites is large, as it is estimated that there are approximately as many parasites as there are species of hosts. As research on human malaria parasites became difficult, Dr. Ross studied avian malaria parasites. Co-speciation and host switching events have contributed to the broad range of hosts that these parasites can infect, causing avian malaria to be a widespread global disease, found everywhere except Antarctica.

<span class="mw-page-title-main">History of malaria</span> History of malaria infections

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<span class="mw-page-title-main">Mosquito-borne disease</span> Diseases caused by bacteria, viruses or parasites transmitted by mosquitoes

Mosquito-borne diseases or mosquito-borne illnesses are diseases caused by bacteria, viruses or parasites transmitted by mosquitoes. Nearly 700 million people get a mosquito-borne illness each year, resulting in over 725,000 deaths.

Pregnancy-associated malaria (PAM) or placental malaria is a presentation of the common illness that is particularly life-threatening to both mother and developing fetus. PAM is caused primarily by infection with Plasmodium falciparum, the most dangerous of the four species of malaria-causing parasites that infect humans. During pregnancy, a woman faces a much higher risk of contracting malaria and of associated complications. Prevention and treatment of malaria are essential components of prenatal care in areas where the parasite is endemic – tropical and subtropical geographic areas. Placental malaria has also been demonstrated to occur in animal models, including in rodent and non-human primate models.

Plasmodium coatneyi is a parasitic species that is an agent of malaria in nonhuman primates. P. coatneyi occurs in Southeast Asia. The natural host of this species is the rhesus macaque and crab-eating macaque, but there has been no evidence that zoonosis of P. coatneyi can occur through its vector, the female Anopheles mosquito.

Thioester containing protein 1, often called TEP1 is a key component of the arthropod innate immune system. TEP1 was first identified as a key immunity gene in 2001 through functional studies on Anopheles gambiae mosquitoes.

<i>Plasmodium</i> helical interspersed subtelomeric protein

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General information about (the biology of) P. berghei
Information about the genome and genes of P. berghei