Sunday, May 29, 2016

Phage Therapy: Using Bacteriophages As Targeted Antibacterials

"We isolated a lytic bacteriophage, OMKO1, (family Myoviridae) of Pseudomonas aeruginosa that utilizes the outer membrane porin M (OprM) of the multidrug efflux systems MexAB and MexXY as a receptor-binding site. Results show that phage selection produces an evolutionary trade-off in MDR P. aeruginosa, whereby the evolution of bacterial resistance to phage attack changes the efflux pump mechanism, causing increased sensitivity to drugs from several antibiotic classes."
A virus found in a pond in Connecticut could help kill lethal superbugs that infect wounds and severe burns, according to new research.

The virus, which is a type of bacteriophage, a name that means “devourer of bacteria”, was discovered by Yale University scientists in Dodge Pond in East Lyme, according to a paper in the journal Scientific Reports.

They discovered that the virus, called OMKO1, attacks a type of multi-drug resistant bacteria that can cause the death of people with damaged immune systems.

Antibiotics and bacteria have become involved in an evolutionary arms race. As bacteria are killed off by the drugs, new strains emerge that can survive them. However, it is thought the bacteria might not be able to evolve to avoid the effects of the phage, weakening them to such an extent that the antibiotics are effective.

Professor Paul Turner, the chair of the ecology and evolutionary biology department at Yale, said: “We have been looking for natural products that are useful in combating important pathogens.
“What’s neat about this virus is it binds to something the organism needs to become pathogenic [disease-causing], and backs it into an evolutionary corner such that it becomes more sensitive to currently failing antibiotics.”

The bacteria attacked by the phage, called Pseudomonas aeruginosa, make their own antibiotics to fight off the antibiotic drugs designed to kill it.

But the Dodge Pond phage attaches itself to the cell membrane where the bacteria pump out its antibiotics. This causes changes in the membrane that makes this pumping mechanism less efficient, the researchers found.

The virus should help preserve our limited antibiotic arsenal in combating deadly bacteria, Professor Turner said.

P. aeruginosa infections affect patients with severe burns, surgical wounds, cystic fibrosis and other conditions that compromise the immune system.

Professor Turner added that other phages appeared to offer hope of creating new ways to combat bacterial pathogens that affect animals and crops in agriculture and contaminate pipes and equipment used in food production.

The tail of bacteriophage T4 is shown before (left) and after (right) binding to a host cell.

More information:
» "the use of viruses as biocontrol agents to combat pathogenic or nuisance bacteria"
» Alexander Sulakvelidze, Zemphira Alavidze, and J. Glenn Morris, Jr., 2001: "Bacteriophage Therapy"

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