"We believe that the drugs exported by these pumps may actually be similar in structure to molecules involved in communicating," said Dr. Lynn Zechiedrich, assistant professor of molecular virology and microbiology at BCM. Thus, the drugs get exported by bacterial cells as if they were the usual communication molecules the cells use to transmit information in a bacterial colony.
While giving a patient a drug starts the process, the bacterial cell is "going down some natural pathway of cell-to-cell communication. It's trying to communicate, and when it does, it increases the number of the pumps to try to send out the molecules. The doctor is trying to kill the bacterial cells with drugs, but the cells just make more pumps to communicate better. The effect is that they get rid of the drug," said Zechiedrich.
Instead of bacterial pumps sending out the usual communication signals, they send out drug instead – inadvertently blocking the ability of the drug to kill the bacteria. This does not occur because the bacteria "know" that the drugs are going to kill them, but because the drug looks like a communication signal. So the bacterial cells send out what they think is a communication signal, which is bad news for doctors and their patients. This process, known as multidrug resistance, results in the failure to cure the bacterial disease. Even worse, the resistance is not just to one drug, but many because the pump is now increased and many different drugs will be pumped out.
"It compounds the problem," said Zechiedrich. Her findings are a step toward understanding the mystery surrounding drug resistance, she said.
In her work, she found that two of these "pumps" or transporters – AcrAB/TolC and NorE – actually export as yet unidentified signals used in cell-to-cell communication.
Dr. Shirley Yang and Graduate student, Christopher Lopez, of BCM, both contributed to the work.
Proceedings of the National Academy of Sciences