Cholera discovery could revolutionize antibiotic delivery

Oct 19, 2012

(Phys.org)—Three Simon Fraser University scientists are among six researchers who've made a discovery that could help revolutionize antibiotic treatment of deadly bacteria.

Lisa Craig, Christopher Ford and Subramaniapillai Kolappan, SFU researchers in molecular biology and biochemistry, have explained how Vibrio cholerae became a deadly pathogen thousands of years ago.

V. cholerae causes the cholera, which is endemic in many developing countries and can emerge in regions devastated by war and natural disasters. An outbreak following the 2010 earthquake in Haiti has killed at least 7,500 people.

Two genes within V. cholerae's genome make it toxic and deadly. The bacterium acquired these genes when a or bacteriophage called CTX-phi infected it.

The SFU researchers and their colleagues at the University of Oslo and Harvard Medical School propose that a Trojan horse-like mechanism within V. cholerae enabled CTX-phi to invade it.

The CTX-phi latches onto a long, hair-like pilus filament floating on the surface of V. cholerae. The filament then retracts, pulling the toxin-gene-carrying CTX-phi inside the bacterium where it binds to TolA, a protein in the bacterial wall.

The process transforms V. cholerae into a deadly .

The has just published a paper written by the researchers describing the of the CTX-phi protein pIII alone and bound to V. cholera TolA.

The authors recommend that pilus filaments be explored further as a transport mechanism to deliver antibiotics into a bacterium.

"We'd be exploiting the pilus retraction mechanism to introduce antibiotics directly into a cell, bypassing its outer membrane barrier," explains Craig. The SFU associate professor is an expert on the role that pili play in bacterial infections.

"We do have antibiotics for V. cholerae, but these antibiotics also kill in the gut. The idea of using pili as a Trojan horse for antibiotic delivery is new and allows us to specifically and effectively target a given bacterial pathogen."

Craig says her team's discovery of V. cholerae's retractable pili is made all the more exciting by the simplicity of its workings. "We know that other have retractable pili but it'll be much easier to isolate how the mechanism can be used to uptake antibiotics in Vibrio ."

Craig says using pili as an antibiotic delivery mechanism to treat Pseudomonas aeruginosa, a deadly bacterial respiratory infection that hits mainly people with Cystic Fibrosis, could save many lives.

Christopher Ford is a research associate in Craig's lab. Subramaniapillai Kolappan, one of Craig's master's students, recently graduated from SFU.

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nkalanaga
not rated yet Oct 20, 2012
It should be fairly simple to engineer a drug that would work this way. Take the latch from the virus coat, attach it to the drug, and you've got it. Since CTX-phi seems to be specific to V. cholerae, there shouldn't be any effect on other bacteria.
PatUF12
not rated yet Oct 26, 2012
This news blurb is a joke, READ THE DAMN PAPER! They do not say this! The invasion by CTX has been know for 20 years, except for the new structure. Antibiotics are not needed to treat cholera. It's been nearly 100 years that rehydration therapy has been used and keeps the death rate less than 1%. PEOPLE NEED CLEAN WATER, NOT ANTIBIOTICS! Learn how to write about science without sensationalism. The paper is outstanding.
PatUF12
not rated yet Oct 26, 2012
BY the CTX is a prophage, this means it already in the genome of the organism causing the infection. There are billions of bateria secreted by each infected person. The action of the CTX toxin is part of the reason for the symptoms.

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