CONTACT: JENNIFER BROWN
Iowa City IA 52242
(319) 335-9917; fax(319) 384-4638
Release: May 30, 2002
UI study identifies a defense mechanism against biofilm
to antibiotics in chronic bacterial infections is a difficult and sometimes
deadly medical problem. During the development of a chronic infection, bacteria
often undergo what could be called a lifestyle change; instead of living as
individual organisms, the bacteria form community structures known as biofilms
that are like cities of bacteria. Bacteria in biofilms are extremely resistant
to antibiotics. Findings from University of Iowa investigators shed light
on how the body normally prevents biofilm development.
Bacterial biofilms are dense, organized cellular communities
encased in a self-produced slime. Living in groups gives the bacteria properties
that they do not have as individuals. In addition to being highly resistant
to antibiotics, biofilms are also impervious to the body's natural immune
defense system. Examples of biofilm infections include lung infections in
patients with cystic fibrosis, wound infections in patients with diabetes
and burns, heart valve infections (known as endocarditis), as well as most
medical device infections.
"Biofilm infections are a major medical problem,
and our group is looking for new strategies to treat or prevent them,"
said Pradeep Singh, M.D., UI assistant professor of internal medicine. "Though
the human body is constantly exposed to disease-causing bacteria, biofilms
do not normally form unless a person's defenses have been compromised by disease.
This lack of biofilm formation suggested to us that the body might have a
natural anti-biofilm defense mechanism."
In a new study of biofilm formation by the bacterium Pseudomonas
aeruginosa, Singh and his colleagues demonstrate that a component of the body's
innate immune system has this previously unknown defense function. These findings
offer insight into how biofilms form and might suggest new strategies for
preventing biofilms. The study appears in the May 30 issue of the journal
In an effort to track down potential anti-biofilm substances,
the UI team focused on lactoferrin, a component of the body's antibacterial
defense system. The researchers found that bacteria grown in the presence
of small amounts of lactoferrin were unable to develop into biofilms. As a
consequence, these bacteria remained vulnerable to antibiotics and other antimicrobial
"Lactoferrin is present in lung secretions, tears,
saliva, breast milk, and other body fluids that come in contact with bacteria,"
Singh said. "Everywhere this defense is needed, lactoferrin is present
in large quantities."
Using time-lapse microscopy to monitor the motion of bacteria,
the UI researchers discovered that lactoferrin causes P. aeruginosa
bacteria to roam incessantly across a surface instead of forming cell groups
or colonies, the first step in biofilm development. Lactoferrin traps iron,
making it unavailable to the bacteria. Iron is a critical nutrient for bacteria
and is difficult to acquire from the environment. The UI team discovered that
low iron concentrations stimulate a specialized form of bacterial surface
motion that causes the bacteria to continually move around as individuals,
rather than aggregating in groups.
"From the perspective of the host, this may be a
fail-safe defense mechanism. If our laboratory studies reflect what happens
on human surfaces, this defense may keep bacteria that survive initial killing
from forming biofilms," Singh said.
However, Singh explained that the roaming behavior might
also benefit the bacteria.
"Humans choose to build cities near food and other
resources; these bacteria seem to have evolved a similar, although more primitive,
behavior. When they sense iron levels are low, the bacteria keep moving rather
than establishing complex communities in an area where a critical nutrient
is in short supply," he said.
Singh speculated that understanding how bacteria sense
iron levels might allow scientists to manipulate that mechanism and trick
bacteria into thinking that the environment has insufficient iron to support
the development of a biofilm. This strategy might help prevent the formation
of potentially devastating biofilm infections in humans.
In addition to Singh, the UI team included E. Peter Greenberg,
Ph.D., the Virgil L. and Evalyn Shepperd Professor of Molecular Pathogenesis
and UI professor of microbiology, and Michael Welsh, M.D., the Roy J. Carver
Chair in Internal Medicine and Physiology and Biophysics, and a Howard Hughes
Medical Institute Investigator. Matthew Parsek, Ph.D., the Louis Berger Junior
Professor of Civil Engineering at Northwestern University, was also part of
the research team.
The research was supported by the Howard Hughes Medical
Institute, the National Heart, Lung and Blood Institute, the National Institute
of General Medical Science, the Cystic Fibrosis Foundation and the W.M. Keck
University of Iowa Health Care describes the partnership
between the UI Roy J. and Lucille A. Carver College of Medicine and UI Hospitals
and Clinics and the patient care, medical education and research programs
and services they provide. Visit UI Health Care online at www.uihealthcare.com.