For immediate release: August 11, 2004
Contact: Beatrijs Lodde, (301) 594-7560
Most people don't expect to get sick after being admitted to the hospital. But hospital-acquired infections from bacteria-laden catheters are actually fairly common, and many doctors say they have few tools to prevent or treat them.
Now, in what could be an important new lead, researchers show in laboratory studies that a novel enzyme can wipe out the ability of Staphylococcus epidermidis to attach to surfaces. Staph. epidermidis is a frequent contaminant of medical devices, costing the healthcare system billions of dollars each year.
"Our goal is to develop the enzyme as an anti-Staph. epidermidis agent which can be used to treat many different surfaces used in the clinic," said Dr. Jeffrey B. Kaplan, the lead author on the article and a scientist at the New Jersey Dental School in Newark. The study was published in the July issue of Antimicrobial Agents and Chemotherapy.
Kaplan noted that he did not start out studying Staph. epidermidis. He was more interested in Actinobacillus actinomycetemcomitans (Aa), an oral bacterium involved in periodontal, or gum, disease. Kaplan and his coworkers had found in previous work that Aa grows together in a layer that spreads out when cultured in a laboratory plate. At first, the scientists did not understand this spreading phenomenon, since Aa is not motile. But they soon discovered that by secreting a previously unknown enzyme called dispersin B, the bacteria release themselves from the surface and diffuse outwards.
The next question was: How exactly did this enzyme do its job? Since enzymes work like scissors that target a specific set of molecules, finding these target molecules might tell them more about dispersin B's function. The researchers already knew that dispersin B cuts polysaccharides (long sugar chains), but they had no idea of which ones in particular. Like many scientists nowadays, they turned to an online database listing known genes and their protein products, in hopes of finding genes involved in the production of a polysaccharide that dispersin B might cleave.
The genomic analysis led them straight to Staph. epidermidis. This bacterium lives on the skin and in mucous areas, such as the nose and mouth, and is the major cause of infected catheters and other medical devices. When, for example, a urinary catheter is inserted into the urethra, Staph. epidermidis can produce a sticky slime that enables them to attach firmly to the instrument, grow into an adherent layer called a biofilm, and ultimately spread to the bladder. Here, the moist, warm environment forms an ideal place for Staph. epidermidis to multiply rapidly.
According to Kaplan, the enzyme could be used as an anti-biofilm agent in different ways. First, it could be coated on catheters to prevent biofilm formation. Additionally, it works on already established biofilms by interfering with their attachment and/or consequently making the bacteria more sensitive to conventional antibiotic therapy.
The researchers showed that pre-coating catheters with dispersin B prevented the formation of a Staph. epidermidis biofilm. This preventive activity lasted for at least a month and showed no signs of enzymatic breakdown, which would make it easy to store the precoated catheters in hospitals until they are needed. The study also demonstrated that dispersin B specifically broke down the slimy substance with lots of polysaccharides, resulting in a detachment of the biofilm. "What is exciting is that by doing basic research on this oral bacterium Aa, we discovered an enzyme that may have potential use as an antibacterial agent in the clinic," said Kaplan.
Looking to the future, Kaplan said the enzyme could be used as an anti-biofilm agent in different ways. First, as shown in the current paper, it could be coated on catheters to prevent biofilm formation. Additionally, he said it could be applied to interfere with the attachment of existing biofilms, as well as make these bacteria more sensitive to conventional antibiotic therapy.
Although Staph. epidermidis is usually not very aggressive, it is resistant to many antibiotics and can lead to persistent infections. From the catheter bacteria can end up in the bloodstream and lead to severe infections and even death, particularly in immunocompromised patients such as premature babies and AIDS patients. More than 80,000 catheter-related bloodstream infections occur in U.S. hospitals each year.
Collaborating with Dr. Kaplan were Drs. Chandran Ragunath, Kabilan Velliyagounder, Daniel H. Fine, and Narayanan Ramasubbu of the Department of Oral Biology, New Jersey Dental School, Newark, New Jersey. The article is titled "Enzymatic Detachment of Staphylococcus epidermidis Biofilms" and was published in Antimicrobial Agents and Chemotherapy in July 2004. The work was supported by the National Institute of Dental and Craniofacial Research.