“Resistance” is a word that makes epidemiologists break into a cold sweat. Unfortunately for you and me, they’ve been hearing it a lot lately, as more antibiotics become less effective. Modern medicine gained the upper hand over disease largely because of the widespread use of broad-spectrum antibiotics. But with increasing drug resistance due to overexposure, that tactic is less likely to remain effective. At some point in the war on disease it may be necessary to switch from the bomb to the rifle, a new generation of narrowly targeted antibiotics.
Marvin Miller believes he has promising approaches to developing some of these microbe-selective drugs. Building on earlier work, the George and Winifred Clark Professor of Chemistry and his colleagues have found a way to exploit a bacterium’s need for iron. Miller’s lab has had some initial success in attaching toxic molecules to certain chemical structures that transport iron only to the disease-causing microbe. When the organism attempts to remove the iron from the transporter, it triggers the release of the poison.
“The organism thinks it’s getting a free lunch,” Miller says. “We provide it with the iron it needs as a nutrient, but when it takes it up, it commits suicide. The microbe triggers the release and its death.”
In related work, Miller’s lab has learned how to modify the iron transport agent used by tuberculosis so it is unable to “digest” iron. Without iron, the organism starves and dies. “Since tuberculosis infects nearly one-third of the world’s population, mostly in Third World countries, and drug resistant strains are emerging, this is a very exciting development for us,” Miller says. The approach holds promise because it is a totally novel way of attacking T.B.
John Monczunski is an associate editor of this magazine.