A Scientific “Chess Game”
.jpg "Richard Calderone examines a test tube with a colleague")
.jpg "Dr. Calderone in his lab")
As new infectious diseases have emerged, older ones, such as polio, malaria, measles, and tuberculosis have still not been eradicated. “Infectious disease is not static; it changes very dramatically and rapidly,” he says.
This quick transformation is especially true in today’s world, where pathogens cross national borders easily within our modern mobile society. As people move into previously uninhabited areas, such as the southwestern desert of the United States, they are exposed to novel microbes, many of which are transmitted by insects or animals. Additionally, as the world warms, pathogens arise to infect people who have not been previously exposed to them.
Now, however, the genomes of a huge variety of microorganisms are available and researchers such as Calderone study these genes to find candidates that are common to a variety of pathogens, such as fungi that cause human disease. Discovery of broad-spectrum drugs to treat these pathogens is one of the ultimate outcomes of such research.
For example, Calderone and his colleagues have identified two proteins from Candida albicans—a form of yeast— called Ssk1 and Chk1. These proteins are required for the organism to cause disease. Both proteins are present in different Candida species and in other fungal pathogens but are absent in humans, suggesting an antifungal drug that inhibits these proteins may not be toxic to patients.
The use of genomics “is an intelligent approach to target identification and drug design,” Calderone says, adding that novel agents to treat fungal infections are needed because they cause many hospital-acquired infections as well as allergic, respiratory, and blood-borne diseases.
Still, Calderone says that, even with all the scientific tools at hand, pathogens may be winning their particular game of microbial chess. That’s because interest by the pharmaceutical industry in developing new agents to treat infectious diseases has steadily fallen; hospital-acquired infections by microorganisms now occur in more than 1.3 million U.S. patients each year.
While academic researchers, including those at GUMC, are increasingly pursuing development of new drugs on their own, they don’t have the massive “libraries” of chemical compounds to identify new compounds that industry has. So the biotechnology industry now plays a major role in anti-infective discovery, he says.
“Nevertheless, to me this is an amazing time in infectious disease research because so much is going on and so much seems possible,” Calderone says. And he is still enamored of the organisms that he has been studying for decades. “They are important to the environment because they are recyclers. Therefore, without fungi and other microorganisms, we’d all be up to the tops of our roofs in nature’s litter,” he says. “They decompose debris and return carbon and nitrogen back into the environment.”
But fungi have become a health scourge, mainly because of modern medicine, he says. Candida on the skin can travel down patient catheters to enter the bloodstream, causing infections that can be particularly troublesome in transplant patients when natural immunity is suppressed, and in people receiving cancer chemotherapy.
Even that is interesting to Calderone.
“Fungi, bacteria, parasites, and viral pathogens are survivors, and each cause disease in their own way,” Calderone says. “Infectious diseases are both old and new and triggered by unimaginable mechanisms.
“The picture changes and persists,” he says. “To the scientist in me, that remains fascinating.”
By Renee Twombly, GUMC Communications
