Research Could Lead to New Non-Antibiotic Drugs to Counter HAIs

Lack of an adequate amount of the mineral phosphate can turn a common bacterium into a killer, according to research to be published in the April 14 issue of the Proceedings of the National Academies of Science. The findings could lead to new drugs that would disarm the increasingly antibiotic-resistant pathogen rather than attempting to kill it.

Pseudomonas aeruginosa is one of the most serious hospital-acquired pathogens. A common cause of lung infections, it is also found in the intestinal tract of 20 percent of all Americans and 50 percent of hospitalized patients in the United States.

It is one of the hundreds of bacteria that colonize the human intestinal tract, usually causing no apparent harm. It might even be beneficial to its host. Once the host is weakened by an illness, surgical procedure or immunosuppressive drugs, however, P. aeruginosa can cause infection, inflammation, sepsis and death.

Why P. aeruginosa can suddenly turn on its host has eluded researchers—until now. Scientists have long known that after an operation or organ surgery, levels of inorganic phosphate fall. The authors of the PNAS paper, led by scientists at the University of Chicago, hypothesized that phosphate depletion in the stressed intestinal tract signals P. aeruginosa to become lethal.

To test this theory, they let worms (Caenorhabditis elegans) feed on "lawns" of P. aeruginosa and Escherichia coli grown in both low-phosphate and high-phosphate media. Only the worms that ate P. aeruginosa with low levels of phosphate died. The researchers dubbed the phenomenon "Red Death" since unexpected large red spots appeared on the worms before they died.

"These findings provide novel insight into the mechanisms by which P. aeruginosa is able to shift from indolent colonizer to a lethal pathogen when present in the intestinal tract of a stressed host," said Alexander Zaborin, lead author of the study and a research professional at the University of Chicago’s Department of Surgery.

"It's almost as if the bacterium sense when to strike," said John Alverdy, corresponding author of the study and professor of surgery at the University of Chicago Medical Center. "That should come as no surprise since the bacteria are smart, having been around for 2 billion years."