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 A promising target for kidney fibrosis
21.04.2017 | Brigham and Women's Hospital

nachricht Stem cell transplants: activating signal paths may protect from graft-versus-host disease
20.04.2017 | Technische Universität München

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: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

DGIST develops 20 times faster biosensor

24.04.2017 | Physics and Astronomy

Nanoimprinted hyperlens array: Paving the way for practical super-resolution imaging

24.04.2017 | Materials Sciences

Atomic-level motion may drive bacteria's ability to evade immune system defenses

24.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>