Understanding the nature of infections

St. Jude Children's Research Hospital (ALSAC)
Monday, 20 August 2001

St. Jude researcher publishes paper in American Scientist

(Memphis, TN, August 20, 2001) A scientist from St. Jude Children's Research Hospital co-authored an article appearing in the September-October issue of American Scientist magazine. In "Pathogens, Host-Cell Invasion and Disease," cell physiologists Erich Gulbins, M.D., Ph.D., and Florian Lang, M.D., report that understanding intricate chemical warfare between host cells and stealthy invaders could lead to the development of a new category of drugs that help cells resist infection.

Gulbins and Lang report that if a pathogen, like a virus or bacteria, can be prevented from entering and hiding in host cells, it will be visible to the immune system and killed by the body's own defense mechanisms. Pathogens are also less likely to evolve resistance to drugs that work in this way.

Gulbins is an associate member of the department of immunology at St. Jude in Memphis, Tenn., and Lang is professor and chair of physiology at the University of Tübingen in Germany. In American Scientist, the investigators review what recent research has revealed about the interaction between host cell and pathogen and its implications for drug development.

No matter how a pathogen enters the body—via the respiratory or the digestive tract, an injury or an insect bite—it faces an army of immune cells that are specialized to devour invading pathogens, shower them with toxic chemicals, punch holes into their cell membranes or bombard them with antibodies that mark them for destruction.

In fact, this defense system is so effective that most people spend much of their lives free of infectious disease, despite daily exposure to countless viruses, bacteria and infectious parasites.

But pathogens, having the advantage of larger numbers, can overwhelm the host's immune system and often adapt more nimbly. Mutation and selection have provided them with mechanisms for circumventing or countering the immune system's attacks. Many pathogens, notably viruses but also many bacteria and infectious eukaryotic parasites (such as the protozoan that causes malaria), invade host cells as a first step so that they are hidden from the immune system as they multiply.

Invasion is not a one-sided process. It often requires the active participation and cooperation of the host. The properties of both host and pathogen determine whether the pathogen can successfully establish an infection or whether it is killed by the host.

Gulbins and Lang said that research on the host-cell internalization process has provided the rationale for development of drugs aimed at blocking a pathogen's entry into a healthy cell rather than targeting the pathogen itself, as in the case of antibiotics. Denied entry into a host cell, the pathogen would have nowhere to hide from the body's natural defenses.

"Treatments based on this concept include small molecules that block the surface structures that attach to target cells and block their ability to trigger internalization," the authors said. A number of biotechnology companies have already developed such anti-infectives that are currently in clinical trials to test their ability to prevent and cure bacterial infections.

"Investigators hope that strengthening the host's defenses, rather than attacking the pathogens directly, will provide therapies against infectious disease that are more durable over the long term than those offered by antibiotics," the article states.

American Scientist is an illustrated bimonthly magazine of science and technology published by Sigma Xi, The Scientific Research Society.

St. Jude Children's Research Hospital, in Memphis, Tennessee, was founded by the late entertainer Danny Thomas. The hospital is an internationally recognized biomedical research center dedicated to finding cures for catastrophic diseases of childhood. The hospital's work is supported through funds raised by the American Lebanese Syrian Associated Charities (ALSAC). ALSAC covers all costs not covered by insurance for medical treatment rendered at St. Jude Children's Research Hospital. Families without insurance are never asked to pay.

For more information, or to contact St. Jude Children's Research Hospital (ALSAC), see their website at: www.stjude.org