Posts Tagged ‘Parasitology’

Why Bees Need Their AMPs

Tuesday, October 1st, 2013

Bee Bumblebees, amongst the most important of pollinators, are under enormous population pressures. One of these is disease. The bumblebee and its gut trypanosome Crithidia bombi are one of the fundamental models of ecological immunology. Although there is previous evidence of increased immune gene expression upon Crithidia infection, recent work has focussed on the bumblebee’s gut microbiota. By knocking down gene expression using RNAi, Leicester research shows for the first time that antimicrobial peptides (AMPs) have a functional role in anti-Crithidia defense.

 

Antimicrobial peptides play a functional role in bumblebee anti-trypanosome defense. (2013) Dev Comp Immunol. doi: 10.1016/j.dci.2013.09.004

 

Scabies

Tuesday, August 13th, 2013

Scabies mite Scabies is a skin disease caused by infestation with the mite Sarcoptes scabiei var. hominis. Closely related species of mite cause mange in animals. Although not fatal, scabies causes considerable morbidity (illness) through direct effects and occasional and mortality as a result of secondary bacterial infections.

Although it occurs worldwide, scabies is a truly neglected disease, largely absent from the global health agenda, and its huge burden of disease is largely underappreciated. Children in developing countries are most susceptible, with an average prevalence of 5–10%. The highest incidence is in tropical climates, with rates of up to 25% overall and up to 50% in some communities in the South Pacific and northern Australia. Poverty and overcrowding are the main risk factors, and outbreaks in institutions and refugee camps are common. Scabies causes intense itch, severely affecting sleep and quality of life. Crusted scabies, a severe infestation with thousands of mites, is associated with extremely high risk of contagion and causes considerable morbidity due to secondary bacterial infections.

Management of scabies is centred on identification and treatment of cases and household contacts, but there is little data to support this as an effective strategy for reducing scabies prevalence. Diagnosis can be difficult and is reliant on clinical identification in most tropical areas. Topical treatments are effective, but the most effective of these, permethrin, is relatively expensive and unavailable in many high-prevalence areas.

The International Alliance for the Control of Scabies (IACS) is a recently formed group from across the globe to advance the agenda of scabies control. The alliance is committed to the control of human scabies infestation, and to promoting the health and well-being of all those living in affected communities. Initial membership includes a diverse range of professionals including clinicians from high-prevalence areas, public health physicians, policy makers, and researchers studying the biology of the parasite, and continues to grow with identification and recruitment of further collaborators.

 

Toward the Global Control of Human Scabies: Introducing the International Alliance for the Control of Scabies. (2013) PLoS Negl Trop Dis 7(8): e2167. doi:10.1371/journal.pntd.0002167

 

Babesia: An Emerging Infectious Threat

Monday, July 22nd, 2013

BabesiosisNever heard of Babesia? Don’t worry, you will soon.

Babesiosis is an emerging zoonosis caused by protozoan parasites of the genus Babesia. In many ways, the organism is similar to the parasites which cause malaria. Although most clinical cases have been reported on the USA, species of Babesia capable of causing disease occur worldwide. In humans, babesiosis causes a broad range of symptoms, broad, ranging from clinically silent infections with no outward signs of infection to intense malaria-like episodes resulting occasionally in death. When present, symptoms typically are nonspecific (fever, headache, and muscle pains).

Babesiosis has long been recognized as an economically important disease of cattle and is transmitted to humans by ticks which feed on cattle asnd then subsequently on a human host. But there are approximately 5 million people who receive blood donations in the USA each year, and the transmission of babesiosis is increasing – it’s not always possible to tell if a blood donor is infected as many have no symptoms. There are currently no good laboratory tests which are cost-effective to use for screening blood donations, so presently a questionnaire is used to try to screen out the highest risk donors.

There are drugs avavilable which treat this infection, although there are also signs that drug resistance may be emerging. You’ll be hearing more about Babesia over the next few years.

Babesia: An Emerging Infectious Threat in Transfusion Medicine. (2013) PLoS Pathog 9(7): e1003387. doi:10.1371/journal.ppat.1003387

Malaria infected mosquitoes are more attracted to human odor

Thursday, May 16th, 2013

Mosquito Mosquitoes infected with the malaria parasite Plasmodium falciparum are significantly more attracted to human odors than uninfected mosquitoes.

Researchers investigated the response of mosquitoes infected with P. falciparum malaria parasites and uninfected to human odor collected on fabric. Mosquitoes that were infected with the parasites landed and probed significantly more than uninfected mosquitoes in response to the odor. Previous research has already shown that the malarial parasite can alter mosquito behavior in ways that increase the rate of malaria transmission. For example, malaria-infected mosquitoes also consume larger, more frequent blood meals than their uninfected counterparts.

Studies of mosquito behavior in the context of malaria transmission usually use uninfected mosquito subjects. This study suggests that such behavioral studies may not always be representative of the behavior of infected mosquitoes. They conclude that understanding the olfactory changes underlying the behavior of these infected mosquitoes may help identify new compounds that could be used to develop mosquito traps for surveillance programs.

 

Malaria Infected Mosquitoes Express Enhanced Attraction to Human Odor. (2013) PLoS ONE 8(5): e63602. doi:10.1371/journal.pone.0063602
There is much evidence that some pathogens manipulate the behaviour of their mosquito hosts to enhance pathogen transmission. However, it is unknown whether this phenomenon exists in the interaction of Anopheles gambiae sensu stricto with the malaria parasite, Plasmodium falciparum – one of the most important interactions in the context of humanity, with malaria causing over 200 million human cases and over 770 thousand deaths each year. Here we demonstrate, for the first time, that infection with P. falciparum causes alterations in behavioural responses to host-derived olfactory stimuli in host- seeking female An. gambiae s.s. mosquitoes. In behavioural experiments we showed that P. falciparum-infected An. gambiae mosquitoes were significantly more attracted to human odors than uninfected mosquitoes. Both P. falciparum-infected and uninfected mosquitoes landed significantly more on a substrate emanating human skin odor compared to a clean substrate. However, significantly more infected mosquitoes landed and probed on a substrate emanating human skin odor than uninfected mosquitoes. This is the first demonstration of a change of An. gambiae behaviour in response to olfactory stimuli caused by infection with P. falciparum. The results of our study provide vital information that could be used to provide better predictions of how malaria is transmitted from human being to human being by An. gambiae s.s. females. Additionally, it highlights the urgent need to investigate this interaction further to determine the olfactory mechanisms that underlie the differential behavioural responses. In doing so, new attractive compounds could be identified which could be used to develop improved mosquito traps for surveillance or trapping programmes that may even specifically target P. falciparum-infected An. gambiae s.s. females.

 

Chlamydia pneumoniae: modern insights into an ancient pathogen

Wednesday, December 19th, 2012

Chlamydia pneumoniae Chlamydia pneumoniae is an enigmatic human and animal pathogen. Originally discovered in association with acute human respiratory disease, it is now associated with a remarkably wide range of chronic diseases as well as having a cosmopolitan distribution within the animal kingdom. Molecular typing studies suggest that animal strains are ancestral to human strains and that C. pneumoniae crossed from animals to humans as the result of at least one relatively recent zoonotic event. Whole genome analyses appear to support this concept – the human strains are highly conserved whereas the single animal strain that has been fully sequenced has a larger genome with several notable differences. When compared to the other, better known chlamydial species that is implicated in human infection, Chlamydia trachomatis, C. pneumoniae demonstrates pertinent differences in its cell biology, development, and genome structure.

This short review examine the characteristic aspects of C. pneumoniae biology, and offers insights into the diversity and evolution of this silent and ancient pathogen.

 

Chlamydia pneumoniae: modern insights into an ancient pathogen. (2012) Trends Microbiol. 05 Dec, doi: 10.1016/j.tim.2012.10.009

Forcing your way in

Wednesday, December 12th, 2012

Apicomplexan Invasion Malaria, toxoplasmosis, and related diseases are caused by infection with unicellular parasites called Apicomplexa. Their name refers to the elaborate invasion machinery that occupies the apical end of the parasite cell. This apparatus allows the parasite to force its way into the cells of its host, and to deliver factors that will manipulate host cell structure, gene expression, and metabolism. Once in the host cell the parasite will begin to grow. The parasite replicates its genome and organelles numerous times and then loads these various elements into numerous daughter cells that will further spread the infection.

This paper describes a fibre that coordinates the daughter cell budding process. The fibre links the centrosome, which controls the mitotic spindle, and the genome with the microtubule organizing center of the budding daughter. Parasite mutants lacking the proteins that build the fiber fail to form daughter cells at the earliest step. The fiber and its components are remarkably similar to fibers that coordinate flagella in algae. While Apicomplexa are not flagelated (with the exception of certain gamete stages) they evolved from flagellated algae. The authors propose that elements of the invasion apparatus evolved from the flagellum or flagellum associated structures.

 

Cell Division in Apicomplexan Parasites Is Organized by a Homolog of the Striated Rootlet Fiber of Algal Flagella. (2012) PLoS Biol 10(12): e1001444. doi:10.1371/journal.pbio.1001444
Apicomplexa are intracellular parasites that cause important human diseases including malaria and toxoplasmosis. During host cell infection new parasites are formed through a budding process that parcels out nuclei and organelles into multiple daughters. Budding is remarkably flexible in output and can produce two to thousands of progeny cells. How genomes and daughters are counted and coordinated is unknown. Apicomplexa evolved from single celled flagellated algae, but with the exception of the gametes, lack flagella. Here we demonstrate that a structure that in the algal ancestor served as the rootlet of the flagellar basal bodies is required for parasite cell division. Parasite striated fiber assemblins (SFA) polymerize into a dynamic fiber that emerges from the centrosomes immediately after their duplication. The fiber grows in a polarized fashion and daughter cells form at its distal tip. As the daughter cell is further elaborated it remains physically tethered at its apical end, the conoid and polar ring. Genetic experiments in Toxoplasma gondii demonstrate two essential components of the fiber, TgSFA2 and 3. In the absence of either of these proteins cytokinesis is blocked at its earliest point, the initiation of the daughter microtubule organizing center (MTOC). Mitosis remains unimpeded and mutant cells accumulate numerous nuclei but fail to form daughter cells. The SFA fiber provides a robust spatial and temporal organizer of parasite cell division, a process that appears hard-wired to the centrosome by multiple tethers. Our findings have broader evolutionary implications. We propose that Apicomplexa abandoned flagella for most stages yet retained the organizing principle of the flagellar MTOC. Instead of ensuring appropriate numbers of flagella, the system now positions the apical invasion complexes. This suggests that elements of the invasion apparatus may be derived from flagella or flagellum associated structures.

Parasite makes mice fearless by hijacking immune cells 

Sunday, December 9th, 2012

The Toxoplasma parasite is an unusually devious operator. When it infects mice, it alters their behaviour so they become fearless enough to seek out cats and get eaten. But exactly how it did this was a mystery. Now it appears that the parasite hijacks its victim’s immune system, causing it to produce a chemical normally found in the brain. The discovery suggests that the brain and immune system might have evolved using similar processes to control their behaviour, including electrical and chemical signals now known mainly in nerves.
New Scientist: http://goo.gl/ScKOQ
PLOS Pathogens:  http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1003051

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How parasitic worms cure inflammatory bowel disease

Friday, November 23rd, 2012

Whipworm Inflammatory bowel disease sufferers (IBD, including Crohn’s disease and ulcerative colitis) experience a variety of unpleasant symptoms such as abdominal pain, vomiting, diarrhoea, rectal bleeding, severe internal cramps/muscle spasms in the region of the pelvis and weight loss. The causes of these diseases are complex and not well understood, but the incidence of IBD is highest in industrialized regions where helminth (parasitic worm) infections have been largely eliminated. This raises the possibility that helminth infections may protect against intestinal inflammation underlying the disease (Inflammatory bowel disease: cause and immunobiology. (2007) The Lancet, 369 (9573), 1627-1640). But no-one wants to be infected with parasitic worms – do they?

IBD is so unpleasant that a number of clincial trials involving deliberate infection of informed volunteers with Trichuris suis have been carried out – with some success (Helminths as governors of inflammatory bowel disease. (2008) Gut, 57(8), 1182-1183). Exactly how the worms help to quell the inflammatory symptoms remained to be completely explained.

Monkeys kept in captivity at Primate Research Centers often develop chronic diarrhoea and bowel disease which shares many features with ulcerative colitis. A new paper tested treatment of captive macaques suffering from this condition with human whipworms. Four out of five treated macaques showed reduced symptoms. After treatment with worms, the monkeys had less bacteria attached to their intestinal wall and a reduced inflammatory response to the gut bacteria. Also, the composition of gut bacteria which was altered in the sick macaques was restored close to the normal flora after treatment with whipworms. These results provide a potential mechanism by which parasitic worms may improve the symptoms of intestinal inflammation, by reducing the immune response against intestinal bacteria.

Immunologic mechanisms underlying the amelioration of colitis

Therapeutic Helminth Infection of Macaques with Idiopathic Chronic Diarrhea Alters the Inflammatory Signature and Mucosal Microbiota of the Colon. (2012) PLoS Pathog 8(11): e1003000. doi:10.1371/journal.ppat.1003000
Young macaques kept in captivity at Primate Research Centers often develop chronic diarrhea, which is difficult to treat because it is poorly understood. This disease shares many features with ulcerative colitis, which is an autoimmune disease affecting the intestinal tract of humans. Recently, parasitic worms have been used in clinical trials to treat inflammatory bowel diseases in humans with positive results, but very little is known about how worms can improve symptoms. We performed a trial where we treated macaques suffering from chronic diarrhea with human whipworms, collecting gut biopsies before and after treatment. We found that 4 out of the 5 treated macaques improved their symptoms and studied the changes in their gut immune responses, as they got better. We found that after treatment with worms, the monkeys had less bacteria attached to their intestinal wall and a reduced inflammatory response to the gut bacteria. Additionally, the composition of gut bacteria was altered in the sick macaques and was restored close to normal after treatment with whipworms. These results provide a potential mechanism by which parasitic worms may improve the symptoms of intestinal inflammation, by reducing the immune response against intestinal bacteria.

 

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Toxoplasma – all your cells are belong to us

Thursday, August 16th, 2012

Toxoplasma gondii Toxoplasma gondii is an intracellular parasite that infects warm blooded animals, including humans. In these hosts, Toxoplasma establishes a chronic infection in the brain, which the parasite accomplishes in part by injecting effector proteins, which manipulate many cellular processes, into cells it invades. Two recent reports suggested that Toxoplasma may also inject effector proteins into cells it does not invade. To look for these “uninfected-injected” cells, researchers utilized three different reporter systems that are tied to injection of effector proteins and not to invasion. They showed that Toxoplasma injects proteins into cells it does not invade and enough protein is injected to manipulate the uninfected cells in a manner consistent with what occurs in infected cells.

Using one of the reporter systems in mice showed that uninfected-injected cells can include systemic immune cells and neurons in the brain. Remarkably, in the brain, the uninfected-injected cells out-number the infected cells by many fold. Together, these results strongly suggest that Toxoplasma manipulates far more cells than previously realized and, given their abundance, these uninfected-injected cells may play a central role in how Toxoplasma engages the host’s immune response.

 

Toxoplasma Co-opts Host Cells It Does Not Invade. (2012) PLoS Pathog 8(7): e1002825. doi:10.1371/journal.ppat.1002825
Like many intracellular microbes, the protozoan parasite Toxoplasma gondii injects effector proteins into cells it invades. One group of these effector proteins is injected from specialized organelles called the rhoptries, which have previously been described to discharge their contents only during successful invasion of a host cell. In this report, using several reporter systems, we show that in vitro the parasite injects rhoptry proteins into cells it does not productively invade and that the rhoptry effector proteins can manipulate the uninfected cell in a similar manner to infected cells. In addition, as one of the reporter systems uses a rhoptry:Cre recombinase fusion protein, we show that in Cre-reporter mice infected with an encysting Toxoplasma-Cre strain, uninfected-injected cells, which could be derived from aborted invasion or cell-intrinsic killing after invasion, are actually more common than infected-injected cells, especially in the mouse brain, where Toxoplasma encysts and persists. This phenomenon has important implications for how Toxoplasma globally affects its host and opens a new avenue for how other intracellular microbes may similarly manipulate the host environment at large.