Learning How Bacteria Build Their Defenses

William Parks, PhD

A new study co-authored by a Cedars-Sinai lung expert sheds light on how certain infectious bacteria resist antibiotic therapy. The findings could lead to new approaches to combating chronic infections, especially in patients with cystic fibrosis, one of the most common fatal genetic diseases in the U.S.

The study, published in the journal Cell Host & Microbe, investigated the formation of biofilms, which are communities of bacteria encased in a matrix of organic compounds known as polymers. These biofilms allow infectious bacteria to survive in tissues such as the lung and skin, where they can produce lingering infections, or cling to medical devices such as catheters, where they can spread disease to other patients.

While biofilms are familiar to scientists, just how the bacteria construct the matrix has been a mystery — until this new study by William Parks, PhD, scientific director of the Cedars-Sinai Women’s Guild Lung Institute, and colleagues at four other institutions.

The secret lies in filamentous bacteriophage, a type of virus that infects and replicates in bacteria. The virus is produced in large amounts when biofilm communities are created. In a series of experiments, the researchers found that these viruses piece together the polymers into highly ordered, liquid crystals. The resulting structures shelter the bacteria and help them resist attacks by antibiotics.

In addition, when the viruses interact with a variety of polymers in the patient's body, the liquid crystal matrix makes the bacterial communities more viscous and resistant to drying up. These changes could contribute to worsening infections, such those seen in cystic fibrosis, as well as contaminating medical devices, Parks said.

The study focused on Pseudomonas aeruginosa, a major bacterial pathogen that causes about 10 percent of hospital-related infections. This bacterium also is responsible for many serious and fatal infections in the airways of cystic fibrosis patients, who tend to develop thick, sticky mucus that clogs their lungs and makes it easier for bacteria to grow. Affecting about 30,000 people in the U.S., cystic fibrosis has no known cure.

The investigators said their in vitro findings suggest that targeting the virus interaction with polymers could eventually provide a new way to combat bacterial infections. "Potentially, such therapies could reduce the transmission of hospital-related infections and help more cystic fibrosis patients avoid chronic lung infections," Parks said.

To advance their research, Parks and his team plan to use animal models to assess how the filamentous bacteriophage promotes bacterial colonization in lungs. "We'd like to see if immunization against the bacteriophage would be effective in preventing the infections in the first place because the immune system would be ready for them," Parks said. Because many other bacteria besides P. aeruginosa build biofilms, the findings could have broader applications, he added.

Parks, a professor of medicine and biomedical sciences, was co-senior author of the study, along with Paul Bollyky, MD, PhD, assistant professor of infectious diseases at Stanford University in Stanford, California. Patrick Secor, PhD, a senior fellow in microbiology at the University of Washington in Seattle, was the lead author. Researchers from the California Institute for Medical Research in San Jose and the Benaroya Research Institute in Seattle also contributed.