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New means of fighting bacterial infection
With bacteria continuing to build resistance to antibiotics, a Miami University Middletown microbiologist is working to stop bacterial infections at an earlier stage in the process--and in a way that discourages the development of resistance.
Marjorie Kelly Cowan, associate professor of microbiology and associate executive director for academic affairs at Miamis Middletown campus, and Benjamin Davis of the University of Oxford, England, developed a homing mechanism that guides an enzyme to the exact protein that the bacterium Actinomyces naesulundii uses to bind to host tissue. The enzyme destroys it before the bacteria can use it for attachment.
This targeted approach is valuable, says Cowan, because if it becomes available therapeutically, the mechanism can be used in much lower concentrations-perhaps up to one million times lower-than blocking agents currently being tested as antimicrobial blocking agents. These chemical blockers have been tested to treat stomach ulcers and bladder infections-so far, with mixed results.
Hugely beneficial in this new approach is the decreased likelihood that the bacteria will become resistant to this type of mechanism. Normally bacteria grow resistant by changing the target that antibiotics bind to, explains Cowan. But adhesion proteins like the one Cowan and Davis have targeted are under evolutionary pressure not to change, since they are vital for the colonizing activity of the bacterial cell. Furthermore, the blocking mechanism will not kill the bacteria, removing another pressure leading to antibiotic resistance.
This is a terrific example of collaboration, says Cowan, who has researched anti-adhesins for years. It took the whole group to get this done: there were essentially four things that had to happen: a) decide to target the adhesion step of infection, b) find an enzyme to degrade the adhesive structure, c) have the idea to put the homing molecule on the enzyme, and d) get the homing molecule made. It took every one of us on the team. And that last step, performed by Ben and the group at Oxford, was by far the toughest.
The team led by Davis and Cowan also consisted of scientists from the University of Toronto and Genencor International, a biotech company in California.
Cowan and Davis are lead authors of Glycodendriproteins: A Synthetic Glycoprotein Mimic Enzyme with Branched Sugar-Display Potently Inhibits Bacterial Aggregation in the March 25 online issue of Journal of the American Chemical Society. The mechanism they developed is an enzyme paired with a sugar known as a "glycodendriprotein."
The article is also featured in the ACSs Chemical and Engineering News, pubs.acs.org/cen/news/8215/8215notw1.html and will be included in its 2004 Year Highlights Issue.