25 September 2012

Antibiotic oomph: the eyes have it

by Will Parker

Berkeley scientists have found that small fragments of a keratin protein in the eye are exceptionally efficient at killing off pathogens, a discovery the researchers believe could lead to new and inexpensive antimicrobial drugs. Details of cytokeratin 6A's antimicrobial properties appear in the Journal of Clinical Investigation.

The researchers, led by Suzanne Fleiszig, came upon cytokeratin 6A in their efforts to solve the mystery behind the eye's remarkable resilience to infection. They noticed that the surface of the eye, unlike other surfaces of the body, did not have bacteria living on it, and that corneal tissue could wipe out a barrage of pathogens in lab culture experiments.

"It is very difficult to infect the cornea of a healthy eye," said Fleiszig. "We've even used tissue paper to damage the eye's surface cells and then plastered them with bacteria, and still had trouble getting bacteria to enter the cornea."

In the hunt for this mystery compound, the researchers cultured human corneal cells and exposed them to the P. aeruginosa bacteria. They then used mass spectrometry to sort out which peptides were most active in fighting off the bacteria. Cytokeratin 6A-derived peptides emerged the winners, and surprisingly, peptide fragments as short as 10 amino acids were effective. Further experiments showed that cytokeratin 6A stopped the bacteria by causing the bacterial membranes to leak, killing the pathogen within minutes.

Already, the scientists have created synthetic versions of these keratin fragments and tested them against an array of pathogens. The synthetic molecules stopped the bacterial strains that can lead to flesh-eating disease and strep throat (Streptococcus pyogenes), diarrhea (Escherichia coli), staph infections (Staphylococcus aureus) and cystic fibrosis lung infections (Pseudomonas aeruginosa). Importantly, the researchers report that the synthetic keratin fragments are relatively easy to manufacture, making them good candidates for low-cost therapeutics.

"We used to think that cytokeratins were primarily structural proteins, but our study shows that these fragments of keratin also have microbe-fighting capabilities," said co-researcher Connie Tam. "Cytokeratin 6A can be found in the epithelial cells of the human cornea as well as in skin, hair and nails. These are all areas of the body that are constantly exposed to microbes, so it makes sense that they would be part of the body's defense."

The researchers noted that further research could reveal numerous different keratin fragments in the body's innate defense system. "Keratins may represent a novel class of antimicrobials with the potential to be designed to selectively kill specific pathogens," said Tam.

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Source: University of California Berkeley