Bacterial gene 'therapy' to combat cholera

Jul 09, 2012
Bacterial gene ‘therapy’ to combat cholera
Credit: Thinkstock

Cholera is an extremely virulent intestinal infection caused by ingestion of the bacterium Vibrio cholerae (V. cholerae). EU researchers elucidated the molecular mechanisms behind expression of virulence genes with important implications for new therapies.

Cholera causes severe diarrhoea and vomiting and the ensuing often results in death within hours. Currently, it is treated with a combination of rehydration therapy and antibiotics.

However, a sort of Darwin’s ‘survival of the fittest’ (or most virulent, in this case) takes place, with the bacteria immune to antibiotics surviving to reproduce. The result is a continuous need to develop new therapies to overcome bacterial resistance to existing antibiotics.

Bacteria have a variety of mechanisms to control gene expression via ribonucleic acid (RNA) molecules. V. Cholerae has its own, among them the quorum regulatory RNAs (Qrrs), four small regulatory RNAs (sRNAs) that control expression of virulence genes and thus the cycle of infection.

At the early stage of infection (low cell density in the host), Qrrs are in high number. They bind to specific messenger RNA (mRNA) targets with the help of the RNA binding protein Hfq, leading to expression of virulent genes.

With rising cell density, Qrrs are no longer produced, virulence-gene expression is turned off and the bacteria are released from the host for reinfection.

European researchers supported by funding of the ‘Investigating sRNAs as the master on/off switch of vibrio cholerae virulence’ (VCSRNAHV) project investigated the molecular processes that lead to expression of virulent genes in order to develop ways to inhibit the process and disarm the bacteria.

Cloning the helper molecule Hfq from V. cholerae facilitated elucidation of its molecular structure and identification of mechanisms leading to enhanced resistance to destabilising conditions.

They also determined the ratio or stoichiometry in which Hfq binds to Qrr molecules (one to one), the location of binding on Qrr and changes in the Qrr molecule subsequent to binding. Finally, the team developed a novel assay that enabled determination of preferences in terms of which Qrr bound to which mRNA target.

is a killer, particularly in developing countries, and its increasing resistance to conventional antibiotics is making its treatment more problematic. The elucidation of underlying expression of in V. cholerae should have important impact on design of novel and effective therapies.

Explore further: Microbes provide insights into evolution of human language

add to favorites email to friend print save as pdf

Related Stories

Evolution of virulence regulation in Staphylococcus aureus

Oct 09, 2008

Scientists have gained insight into the complex mechanisms that control bacterial pathogenesis and, as a result, have developed new theories about how independent mechanisms may have become intertwined during evolution. The ...

Researchers work towards pharmacological targets for cholera

Jan 20, 2011

Just over a year after the earthquake in Haiti killed 222,000 people there's a new problem that is killing Haitians. A cholera outbreak has doctors in the area scrambling and the water-borne illness has already claimed 3600 ...

Recommended for you

Cell division speed influences gene architecture

13 hours ago

Speed-reading is a technique used to read quickly. It involves visual searching for clues to meaning and skipping non-essential words and/ or sentences. Similarly to humans, biological systems are sometimes ...

Secret life of cells revealed with new technique

15 hours ago

(Phys.org) —A new technique that allows researchers to conduct experiments more rapidly and accurately is giving insights into the workings of proteins important in heart and muscle diseases.

In the 'slime jungle' height matters

16 hours ago

(Phys.org) —In communities of microbes, akin to 'slime jungles', cells evolve not just to grow faster than their rivals but also to push themselves to the surface of colonies where they gain the best access ...

Queuing theory helps physicist understand protein recycling

Apr 22, 2014

We've all waited in line and most of us have gotten stuck in a check-out line longer than we would like. For Will Mather, assistant professor of physics and an instructor with the College of Science's Integrated Science Curriculum, ...

User comments : 0

More news stories