Plasmodium berghei

''Plasmodium berghei'' is a species in the genus ''Plasmodium'' subgenus '' Vinckeia''.

It is a protozoan parasite that causes malaria in certain rodents. 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''.

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''.

Immunochemistry

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

Strains

Some strains produce cerebral murine malaria and some do not.
* produces CMM. Martins ''et al.'', 2016 find endothelin-1 production is vital to CMM disease progression. Subramaniam ''et al.'', 2015 find mice respond to ANKA by increasing BTNL2. Chertow ''et al.'', 2015 find arginine metabolism indicative of disease severity.
* notably does not produce CMM. Martins ''et al.'', 2016 find NK65 ''can'' produce CMM under supplementation of endothelin-1.
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.'' In research laboratories, various rodents can be infected, such as mice (''Mus musculus''), rats and gerbils (''Meriones unguiculatus''). In ''M. musculus'' ⇔ ''P. b.'' ANKA, downregulation of responses is necessary to prevent self-inflicted damage leading to CMM. 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.

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

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:
* Apolipoprotein A-I (''APOA1'')
* Low density lipoprotein receptor ('' LDLR'')
* Low density lipoprotein receptor-related protein 1 ('' LRP1'')
* Very low density lipoprotein receptor (''VLDLR'')
They find one improves survival probability:
* Apolipoprotein E (''APOE'')

'' An. gambiae''s hemocytes transcribe a wide array of molecular responses to ''Plasmodium'' infections. NIHMSID 615755. 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.

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.

History

This species was first described by Vincke and Lips in 1948 in the Belgian Congo.Vincke, I.H. and Lips, M. (1948) Un nouveau plasmodium d'un rongeur sauvage du Congo: ''Plasmodium berghei'' n.sp. Annales de la Société Belge de Médecine Tropicale 28, 97-104

Research

''Plasmodium berghei'' infection of laboratory mouse strains is frequently used in research as a model for human malaria. 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.

''Plasmodium 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''. Instead, in ''P. berghei'' infection, mice are found to have an accumulation of immune cells in brain blood vessels. This has led some to question the use of ''P. berghei'' infections in mice as an appropriate model of cerebral malaria in humans.

''Plasmodium 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. 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''.

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.

''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.

References

External links

{{Scholia, topic
;General information about (the biology of) ''P. berghei'':
www.pberghei.nl/homepage/model-of-malaria

;Information about the genome and genes of ''P. berghei'':
www.pberghei.euplasmogem.sanger.ac.ukwww.plasmodb.org/plasmo/appwww.ncbi.nlm.nih.gov/sites/entrez?Db=genomeprj&Cmd=Search&Term=txid5821

berghei
Parasites of rodents