New drug targets. The symposium was organized and chaired by Dr. Elaine Bearer, Brown University Medical School, and co-chaired by Dr. Richard Lynch, Medical School of the University of Iowa. Dr. Bearer’s laboratory was the first to reconstitute human herpes virus transport in vitro. The herpes virus enters the nerve ending in the mucous membrane of the lip or eye and travels inside the nerve back toward the neuronal cell nucleus in the central nervous system. Dr. Bearer's work provided evidence that a single transport mechanism was responsible for this movement. Now, in new work reported at Experimental Biology 2002, Dr. Bearer believes she is coming close to identifying the precise piece of the virus that lets it travel. Once these transport codes are found, she says, it’ll be relatively easy to develop drugs to halt the various herpes viruses in their track, preventing any further symptoms including cold sores, genital herpes lesions, and blindness or death of infants born to mothers with an active genital herpes infection. Looking slightly further down the road, she says that the transporter mechanism will be a good vehicle to carry desired genes to the cellular DNA in gene therapy. Understanding the traffic along neurons also may someday provide insight into the neuronal destruction of Alzheimer’s.
Using viruses to destroy bacteria. Dr. J. Glenn Morris, University of Baltimore, works with hundreds of bacterial viruses able to invade bacterial cells and cause bacteria to self-destruct. With the increase in bacteria resistant to most or all currently available treatments (and the concomitant increase in the number of immunosuppressed patients at particularly high risk for bacterial infection), the need for development of alternative anti-bacterial treatments has become one of modern medicine’s highest priorities. Dr. Morris says bacteriophages (“bacteria eaters”) have some very real advantages. In particular, each bacteriophage is highly specific, attacking only the “bad” bacteria against which it has been selected, leaving “good” bacterial like intestinal flora intact. Bacteriophages don’t hurt humans, and in fact are a routine part of the world in which we live. In contrast to antibiotics, which may require years for development, bacteriophages with activity against new, emerging pathogens (including pathogens used for bioterrorism) often can be identified in a matter of weeks. Until recently, most of the research on bacteriophages has come from Eastern Europe and the former Soviet Union (some of Dr. Morris’s colleagues are from the current generation of former Soviet scientists). are increasing efforts underway to obtain regulatory approval for their testing and use in clinical and environmental settings.
Focusing on the bacterial biofilms where the majority of bacteria grow. It appears even the most troublesome bacteria couldn’t cause all the havoc they do by standing alone. Dr. Heidi Kaplan, University of Texas Medical School, reports on how microbes create and maintain their own environment: biofilms or complex gooey mixtures of extra-cellular molecules that support growth of infectious organisms and alter normal human cellular processes. These biofilm bacteria are a major health concern, says Dr. Kaplan, because the cells within the biofilm can acquire greater than 500-fold (yes, five hundred) resistance to antimicrobials and thus be better able to evade the host cellular immune response, resulting in persistent and chronic human infections. Dr. Kaplan uses the gram-negative pathogen P. aeruginosa as a model for studying biofilm formation, tracking adherence of the bacteria to surfaces, formation of a microcolony, and maturation into a biofilm. P. aeruginosa causes a variety of persistent and chronic infectious diseases, including those in the lungs of cystic fibrosis patients and on the skin of burn patients. Dr. Kaplan’s laboratory has been studying the “twitching” movement in which cells attach to neighboring cells to create the biofilm, and she believes such understanding of how the biofilm forms and functions will identify new targets for the prevention and treatment of chronic and persistent infections.
Learning how to turn on the cell’s natural immune response. MIT’s Dr. Richard Young has been using gene array technology to eavesdrop on the cross talk between invading microbes and the immune cells of our body. His lab has been exploring the responses of human macrophages and dendritic cells to a variety of bacteria. Macrophages and dendritic cells, immune cells that are part of the first line of defense, recognize and engulf microbes in a vigilant effort to keep the body healthy. The researchers found that these cells respond to a broad range of bacteria by sending off an alarm to the rest of the immune system. Further study revealed that the macrophage didn't have to "see" the whole bacteria to send off its alarm signal, but the presence of the specific bacterial components such as heat shock proteins induced the response. This suggests promising new adjuvants (compounds that make a vaccine more potent by increasing an immune response) could be used in vaccine development. “DNA microarray data are proving us with unprecedented details about our own immune defense cells as they orchestrate a response to attacking bacterial pathogens that are responsible for some of the major diseases of mankind,” says Dr. Young. “This information should lead to new therapeutic strategies against these diseases.
Answering basic questions about how bacteria make us sick. During recent years, scientists have begun to understand in great detail how bacteria cause disease, says Dr. Jorge Galan, Yale University Medical School. His own recent work has unraveled the tricks used by the large and ancient family of salmonella bacteria, which are capable of causing a wide range of illnesses from mild food poisoning to life-threatening systemic infections like dysentery and typhoid fever. Because salmonella bacteria have co-existed with vertebrate hosts for perhaps as long as 10 million years, they have had plenty of time to evolve extremely sophisticated mechanisms to interact with host cells. Dr. Galan tracked how the bacterium uses a specialized organelle to inject its own proteins into the host's cell cytoplasm, subverting the cell's life machinery by mimicking normal protein activity in the cell, in some cases representing the result of what he calls "extensive molecular tinkering and convergent evolution."