Friday, September 28, 2012

Flesh-Eating Disease And "Genetic Engineers"

Royal Society University Research Fellow Dr Edward Taylor, from the University of Lincoln’s School of Life Sciences, is carrying out research on bacteriophage that play a role in flesh-eating disease.

Dr Taylor spent the last ten years at the University of York where he was awarded a Royal Society University Research Fellowship in 2006. He has chosen to continue his research at the University of Lincoln, with funding continuing for a further two years.

Phage protein crystals
Credit: University of Lincoln

Bacteriophage (often called phage) are viruses that infect bacteria. These are extremely common and mostly harmless; however some play a role in diseases such as diphtheria, cholera, dysentery, botulism, necrotizing (flesh-eating) pneumonia, toxic shock and scarlet fever.

Phages are nature’s “genetic engineers”, frequently swapping genes between bacterial strains. This happens by the phage attaching itself to the surface of the cell, making a hole and then injecting its own DNA into the bacteria. Occasionally this DNA becomes integrated into the bacterial chromosome where it lays dormant, but more commonly the phage is active straight away. The bacterial metabolism is hijacked, the DNA de-coded and new phages are produced in great numbers. Finally the bacterium is burst open and the new virus particles escape.

This inactive/active life style allows the phage to cleverly separate its outbreaks over long periods of time. Some phage which infect harmful bacteria carry toxin and other genes which when decoded interact with our immune systems, tying them together, giving the phage and bacteria a better chance of survival. Some phages also destroy bacteria.

Dr Taylor works on a particular phage which infects a flesh-eating bacterium called ‘Streptococcus pyogens’. This carries a toxin and DNase genes, which when expressed go on to damage the immune system causing scarlet fever, “toxic shock” and more invasive necrotizing forms of infection.

Dr Taylor said: “This research will allow for a fundamental understanding of bacterial pathogenicity and the role of viruses in disease processes. The overall aim is to carry out an in-depth structural study on one phage that prompts Streptococci to become toxigenic. I am studying complexes of the viral proteins using a technique – known as X-ray crystallography. This enables me to “see” the individual atoms within a protein. I am particularly interested in the mechanism of enzymes which break down DNA. These have been shown to help the Streptococcus pyogenes evade capture by the immune system and promote more invasive necrotizing forms of infection. I am studying these enzymes by making small changes to the protein structure and seeing what effect this has on the way the enzyme works. Through these changes I hope to gain a better understanding of the disease process.”

It was through focused research with Professor Gideon Davis during his time at the University of York that led Dr Taylor to develop his own interests in the interplay between certain pathogenic bacteria and their compatible bacteriophage.

Contacts and sources:
University of Lincoln

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