A new type of antibiotic called a PPMO, which works by blocking genes essential for bacterial reproduction, successfully killed a multidrug-resistant germ common to health care settings, UT Southwestern Medical Center researchers report.
The technology and new approach offer potential promise against the growing problem of antibiotic resistance, the researchers said.
The pathogen (germ) - called Acinetobacter - can cause infections from pneumonia to serious blood or wound infections, posing greater risk to people with weakened immune systems, chronic lung disease, or diabetes, according to the Centers for Disease Control and Prevention (CDC). Acinetobacter infection mainly affects hospitalized patients or those in long-term care facilities, such as those on ventilators or with urinary cathetersor patients treated for open wounds. The CDC considers Acinetobacter, which is resistant to many antibiotics, one of the top bacterial infection threats in the U.S.
In the study in today's Journal of Infectious Diseases, PPMOs peptide-conjugated phosphorodiamidate morpholino oligomer, (link for PMOs only) designed to combat two strains of Acinetobacter reduced the number of infectious bacteria in mice by more than 90 percent. Survival of infected mice also improved with the treatment. One of the targeted strains was A. baumannii, a dangerous type that accounts for about 80 percent of reported Acinetobacter infections, according to the CDC.
"We set out to target specific genes in Acinetobacter in an effort to inhibit the bacterium-s growth," said Dr. David Greenberg, assistant professor of internal medicine and microbiology and senior author of the study. "With infections from drug-resistant pathogens rising rapidly, there is an urgent need to come up with new approaches such as the use of PPMOs to spur antibiotic development."
The technology that created the synthetic PPMO could be used to develop similar antibiotics targeting other bacteria and viruses, he added.
"We believe there is a lot of promise in developing new antibiotics that target specific pathogens as opposed to so-called broad-spectrum antibiotics that target whole classes of bacteria," said Dr. Greenberg.
This paper builds on earlier work describing gene knockdowns in bacteria with Morpholino oligos, mostly from Prof. Geller's lab: http://www.gene-tools.com/node/45 (citations)
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