Potential target to treat sepsis identified

Washington, Feb 29 : Researchers at the University of Illinois at Chicago have identified the enzymes critical for the growth and survival of bacteria in blood - opening a broad path to treatments for severe sepsis.

The disease sepsis is quite severe, fast moving, dramatic, and often fatal. It is caused due to a violent bacterial infection that enters the bloodstream.

Tythe invasion by these bacteria leads to the production of endotoxins and other toxic chemicals initiating a widespread inflammatory response of the innate immune system.

"The growth of bacterial pathogens in blood represents one of the most dangerous stages of infection," said Alexander Mankin, professor and associate director of UIC's Center for Pharmaceutical Biotechnology.

"Before we can discover an antibiotic to treat bloodstream infections, we first had to discover which enzymes are essential for bacteria to live in the bloodstream. Our major goal was to identify genes that are critical for the survival and growth of bacteria in blood," he added.

For the study, Shalaka Samant, a graduate student in Mankin's laboratory, infected human blood in a test tube with E. coli bacteria, a major cause of bloodstream infections in hospitalized patients.

Using a new technique, Samant found that 19 E. coli mutants out of more than 4,000 she tested could not grow in blood. The majority of the mutants carried a deletion of a gene involved in making nucleotides, the building blocks of DNA and RNA.

Samant said the findings showed that the biosynthesis nucleotides is crucial for the growth of the bacteria in human blood.

She studied another bloodstream pathogen -- Bacillus anthracis, the causative agent of anthrax.

"There are few treatment options available for the late stages of anthrax infections. We found that, similar to E. coli, anthracis bacilli that could not biosynthesize nucleotides also were unable to grow in blood," Samant said.

Researchers led by Dr. James Cook, chief of infectious diseases, immunology and internal medicine at the University of Illinois Medical Center at Chicago, added to Samant's research by showing Bacillus anthracis mutants that were unable to synthesize nucleotides were not able to infect mice.

After they were infected with anthrax, the mice remained healthy, with no bacteria detected in their blood.

According to Mankin, the enzymes of nucleotide biosynthesis could make excellent antibiotic targets.

The UIC Center for Pharmaceutical Biotechnology is now working to identify drugs that inhibit these enzymes.

The study is published in the February issue of the journal PLoS Pathogens.

ANI