Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Haiti cholera mutations could lead to more severe disease

16.04.2013
Strain is evolving to be more like virulent 1800s cholera

The cholera strain that transferred to Haiti in 2010 has multiple toxin gene mutations that may account for the severity of disease and is evolving to be more like an 1800s version of cholera, reports a new Northwestern Medicine study.

The strain, "altered El Tor," which emerged around 2000, is known to be more virulent and to cause more severe diarrhea and dehydration than earlier strains that had been circulating since the 1960s. This study reports the altered El Tor strain has acquired two additional signature mutations during the past decade that may further increase virulence.

In addition, these newly discovered signature mutations documented in the study further link the Haitian cholera epidemic to the strain from Nepal.

The paper will be published April 16 in the journal mBio.

The new Northwestern study suggests the strain with multi-signature toxin gene mutations may trigger a unique pattern of infection accounting for the severity of disease noted during the Haiti cholera outbreak.

"The cholera strain from the 1800s epidemic did the same thing," said Karla Satchell, the senior author of the paper and an associate professor of microbiology-immunology at Northwestern University Feinberg School of Medicine. "That strain also modified its toxin genes and the cholera got worse."

Satchell has spent her career studying a single toxin of the bacterium that causes cholera, MARTX, which helps the bacteria block the body's immune defense so cholera can colonize the gut. She closely followed genomics research conducted to track the Haiti epidemic, curious to see how her toxin was affected. She was shocked to see it had completely mutated out of existence.

"Oh, my!" she recalls thinking. "My toxin has been booted out of this key strain." She postulates that this may have affected the behavior of the mutated strain in disease.

Satchell and colleagues analyzed publicly available genomic sequencing data and found this new cholera strain had accumulated some curious genetic changes during its global spread. First, the main cholera toxin that causes the diarrhea acquired genetic changes that converted the toxin to a form similar to that produced by strains prevalent during the historic cholera epidemics of the 1800s.

Surprisingly, this new strain next acquired a genetic lesion that inactivated the MARTX toxin, previously recognized to be important for evading the immune system. A third as yet uncharacterized genetic mutation in the cholera toxin followed, suggesting a mutation emerged in the cholera toxin to compensate for the loss of MARTX.

These mutations occurring in the same strain indicate that the bacterium interacts differently with the immune system than previous strains.

"Perhaps this results in the bacterium more successfully evading early detection after a person accidently drinks cholera infected fluids," Satchell said. "Interestingly, these multiple mutations in important proteins that specifically contribute to disease could explain why this strain is causing more severe disease, although the contribution of each mutation to human infection remains to be studied."

Previously published research on the Haiti cholera strain noted the change in the bacterium's DNA and tracked its origin to Nepal, but scientists didn't ask how the changes affected the bacterium's function. In addition, scientists had believed the bacterial strains responsible for the "new wave" of cholera that engulfed Haiti and first began spreading in 2000 were functionally identical to most other strains prevalent in the environment.

Satchell's finding further confirms the strain infecting Haiti likely originated in Nepal, consistent with the conclusion from the whole genome analysis and public health studies. Strains with this unique signature of a cholera toxin with three genetic changes coupled with loss of MARTX has spread only in a very defined geographical area including India where it was first detected in 2007. It has spread through Bangladesh, Cameroon, Nepal and then into Haiti and the Dominican Republic in 2010. Even though other strains are nearly identical and barely distinguishable at the genetic level, only this very small group of isolates share this unique signature, verifying from a functional viewpoint that the strain that moved to Haiti likely originated in Nepal.

"What we discovered is that the bacterial strains responsible for the 'new wave' of cholera are not all functionally identical with minor modification as previously thought, nor are they similar to most other strains prevalent in the environment, but, in fact, the strain with multi-signature toxin gene mutations may instigate a unique pattern of infection accounting for the severity of disease noted during the Haiti cholera outbreak," Satchell said.

Marla Paul | EurekAlert!
Further information:
http://www.northwestern.edu

More articles from Health and Medicine:

nachricht Serious children’s infections also spreading in Switzerland
26.07.2017 | Universitätsspital Bern

nachricht New vaccine production could improve flu shot accuracy
25.07.2017 | Duke University

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Carbon Nanotubes Turn Electrical Current into Light-emitting Quasi-particles

Strong light-matter coupling in these semiconducting tubes may hold the key to electrically pumped lasers

Light-matter quasi-particles can be generated electrically in semiconducting carbon nanotubes. Material scientists and physicists from Heidelberg University...

Im Focus: Flexible proximity sensor creates smart surfaces

Fraunhofer IPA has developed a proximity sensor made from silicone and carbon nanotubes (CNT) which detects objects and determines their position. The materials and printing process used mean that the sensor is extremely flexible, economical and can be used for large surfaces. Industry and research partners can use and further develop this innovation straight away.

At first glance, the proximity sensor appears to be nothing special: a thin, elastic layer of silicone onto which black square surfaces are printed, but these...

Im Focus: 3-D scanning with water

3-D shape acquisition using water displacement as the shape sensor for the reconstruction of complex objects

A global team of computer scientists and engineers have developed an innovative technique that more completely reconstructs challenging 3D objects. An ancient...

Im Focus: Manipulating Electron Spins Without Loss of Information

Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.

For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...

Im Focus: The proton precisely weighted

What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.

To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

Closing the Sustainability Circle: Protection of Food with Biobased Materials

21.07.2017 | Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

 
Latest News

CCNY physicists master unexplored electron property

26.07.2017 | Physics and Astronomy

Molecular microscopy illuminates molecular motor motion

26.07.2017 | Life Sciences

Large-Mouthed Fish Was Top Predator After Mass Extinction

26.07.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>