Tag Archives: plos pathogens

Pandemic norovirus rapidly evolves to make you vomit

Pandemic noroviruses have a faster rate of evolution than non-pandemic strains, which could explain why they are better adapted to cause worldwide outbreaks of viral gastroenteritis, according to research published free in PLoS Pathogens this week.

...probably not as clean as this if you have a norovirus infection!!

Norovirus is an RNA virus that is responsible for the majority of viral gastroenteritis outbreaks worldwide. Norovirus infection—dubbed ‘winter vomiting disease’—is notoriously associated with cruiseships and can cause havoc in hospitals. Symptoms of norovirus infection include diarrhoea and projectile vomiting, which can spread viral particles easily from person-to-person, on contaminated surfaces or in contaminated food and water. Moreover, the virus is incredibly contagious—only 10 or so viral particles are needed to cause infection—and able to survive for several days in a contaminated area.

Despite the fact that over 40 genotypes of norovirus circulate within a population at the same time, only one, known as genogroup II genotype 4 (GII.4), causes winter vomiting disease pandemics. 62% of worldwide norovirus outbreaks are caused by GII.4 and very little is known about why this particular norovirus genotype causes mass disease outbreaks.

Bull et al. investigated how quickly different norovirus genotypes replicated and mutated, and how this could contribute to the ‘fitness’ of the virus during infection. The researchers used in vitro RNA dependent RNA polymerase assays and bioinformatics data to measure the rates of replication, mutation and evolution for the GII.4 pandemic norovirus compared with rates for the less frequently detected non-pandemic norovirus genotypes (recombinant GII.b/G.III, GII.3 and GII.7), and hepatitis C virus as a control. They found that GII.4 strains of norovirus had much higher rates of mutation, replication and evolution than the other norovirus strains tested. Evolution rates were measured within the viral capsid (the outer protein coat of the virus) and GII.4 strains had more mutations that made changes to the capsid’s amino acid sequence than the other noroviruses.

Bull and colleagues argue that the rapid mutations seen in the GII.4 norovirus make it similar to influenza, in which “an increase in antigenic drift has been associated with increased outbreaks.” The research will help scientists better understand how norovirus causes winter vomiting disease pandemics and could prove useful during development of a vaccine or treatment for norovirus. So just remember this when you’re quarantined in your cruise cabin and upchucking into your toilet—the norovirus has mutated fast to make it ‘fit’ to infect you.

ResearchBlogging.orgBull, R., Eden, J., Rawlinson, W., & White, P. (2010). Rapid Evolution of Pandemic Noroviruses of the GII.4 Lineage PLoS Pathogens, 6 (3) DOI: 10.1371/journal.ppat.1000831

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African trypanosomes just love social networking

The procyclic form of african trypanosomes move together as a group when grown on a semisolid surface, according to new research from US scientists published in the journal PLoS Pathogens. This “social motility” is mediated by their flagellum and is a surprising new feature in trypanosome biology.

The African trypanosome, Trypansoma brucei, is a parasite which causes the disease “sleeping sickness” or African trypanosomiasis. The disease is endemic in regions of Sub-Saharan Africa and causes significant mortality, with estimates suggesting that 50,000-70,000 people are currently infected. The disease is transmitted to humans by bites from tsetse flies which are infected with the parasite. Initially, symptoms include fever and joint pains but once the parasite has entered the brain from the bloodstream it causes the neurological symptoms of the infection which gives the disease its name­—confusion, fatigue and sleep cycle disturbances. Under certain conditions, bacteria can move by various forms of social motility including gliding, swarming and twitching. They are known to group together in multicellular communities in which the bacteria can communicate together to move and respond to external stimuli. Trypansomes on the otherhand are thought to live as single cell entities.

Michael Oberholzer and colleagues studied the growth of procyclic T. brucei on a semisolid agar surface. The researchers found that the parasites grouped into a large multicellular community that could move across the surface of the agar, and could recruit more cells into the heaving mass (see the supporting video S1). They found that the parasite groups moved in a polarised direction and sent out “scout” parasites which moved in and out of the main group to come into contact with neighbouring cells. These scouts then communicated in some way to the main parasite crowd in order to merge new parasites into the main group or avoid them altogether by changing the direction of movement of the group. The investigators then used knockdown parasites which lacked a normal flagellum (a sort of tail on the parasite which helps them to move) and showed that their co-operative movements were mediated by their flagellum.

This research shows an interesting new facet to trypanosome biology and offers an insight into how the parasites behave. It will be interesting to see whether the trypanosomes act in the same way when they have infected humans or tsetse flies, and more research is needed to determine the physiological role of this trypanosome social motility.

ResearchBlogging.orgMichael Oberholzer, Miguel A. Lopez, Bryce T. McLelland, & Kent L. Hill (2010). Social motility in African Trypanosomes PLoS Pathogens, 6 (1) : doi:10.1371/journal.ppat.1000739

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Researchers make first steps towards making a vaccine for urinary tract infections

utiFed up of stocking up on cranberry juice to stave off painful peeing….well researchers from the University of Michigan have made an important step towards making a vaccine to prevent urinary tract infections (UTIs), if the immunity seen in mice can be reproduced in humans. The findings by Alteri and colleagues were published this week in PLoS Pathogens (its open-access so go take a look at the paper for yourself).

UTI is a bacterial infection that affects any part of the urinary tract (including kidneys, ureter, bladder and urethra). They are incredibly common; it is thought 53% of women and 14% of men will experience a UTI during their lifetime. They are significant healthcare burden; in the United States alone, UTIs have an estimated annual cost of $2.4 billion each year. There are two types of UTI. Lower UTIs affect the bladder (cystitis) and urethra (urethritis) with symptoms of a mild fever, the urge to urinate frequently, smelly, bloody or cloudy urine, and that oh so infamous pain or burning sensation when you need to urinate. Upper UTIs affect the ureter and the kidneys (pyelonephritis) and include symptoms of high fever, nausea and vomiting, chills and shaking and localised pain in your lower back. Upper UTIs are potentially more serious since they can cause kidney damage. UTIs can be treated with antibiotics but there is increasing evidence of antibiotic resistance. Furthermore, recurrent infections occur frequently. An estimated 27% of women experience a second infection, and 2.7% of those suffer a third infection, within 6 months from the initial infection. Uropathogenic (pathogens that infect the urinary tract) Escherichia coli (UPEC) is the most likely cause of an uncomplicated UTI and so the researchers wanted to develop a vaccine to prevent infection by these bacteria.

The researchers used large-scale reverse vaccinology (pioneered by Rino Rappuoli and first used for vaccines against meningococci, the bacteria that cause meningitis). This combines bioinformatics, genomics and proteomics, to quickly and efficiently identify proteins in UPEC that are novel vaccine targets. The researchers looked for proteins to act as antigens, substances that would trigger an immune response to produce protective antibodies (a protein which binds foreign antigens to identify and neutralise them). The researchers screened 5,379 predicted bacterial proteins in the UPEC strain E. coli CFT073 and identified six proteins that matched vaccine candidate criteria including proteins that were highly expressed in vivo, specific to pathogens and induced during growth in human urine. The vaccine candidates were all pathogen-associated iron receptors (ChuA, Hma, Iha, IreA, IroN and IutA). These receptors are required for uptake of iron and are present on the surface of the bacteria. Each of the iron receptor proteins were expressed and purified and these antigens were cross-linked to cholera toxin, which acts as an adjuvant (a substance that increases the ability of an antigen to stimulate the immune system). Mice were inoculated with each antigen-adjuvant complex in their nasal passage. The researchers investigated whether mice could be protected from UTI and measured the immune response that occurred in the mice after vaccination.

Vaccination with Hma, IreA and IutA significantly protected mice against colonisation with UPEC strains in the kidneys and bladder. Spleen cells from vaccinated mice significantly secreted IFNγ and IL-17, which are protective proinflammatory cytokines (proteins released by cells which act as signalling molecules and help generate an immune response). Also, mice secrete protective antigen-specific antibodies following vaccination, which correlated with protection against infection with UPEC. Increased levels of IgA (an antibody found in mucous) were measured in urine and high levels of IgM (an antibody part of the primary immune response to a foreign antigen) and IgG (an antibody that is part of the secondary protective immune response) were measured in serum.

Vaccination with iron receptors elicits protective immunity from experimental UTI in mice. Iron receptors are promising vaccine candidates to protect against UPEC infections in humans and future clinical trials will determine whether the immunity seen here can be reproduced in humans. Interestingly, uptake of iron is a critical function required specifically by pathogenic bacteria in order to survive, but often not in commensal bacteria (normally harmless bacteria which are part of our natural microflora on and inside our bodies). Vaccines that include iron receptors could be used to prevent infections by other pathogenic bacteria. Also, the researchers show that vaccination in nasal mucous membranes induces an immune response in mucosal tissue elsewhere in the body, in this case the urinary tract. Although a successful UTI vaccine may be a long way off this paper details key research which should help its development.


Both these webpages give detailed info on symptoms, diagnosis and treatment of UTIs:

Medline Plus topic page on UTIs

http://www.nlm.nih.gov/medlineplus/urinarytractinfections.html

NHS direct topic page on UTIs

http://www.nhs.uk/conditions/Urinary-tract-infection-adults/Pages/Introduction.aspx

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