Researchers find gene mutation that helps bacteria tolerate antibiotics

MEMPHIS, Jan. 3 (UPI) -- Researchers at St. Jude Children's Research Hospital uncovered a gene mutation that allows bacteria to tolerate normally effective antibiotic therapy.

Doctors at St. Jude were treating a 6-week-old infant for acute myleoid leukemia when the infant developed an infection in her blood stream called vancomycin-resistant Enterococcus faeclum, or VRE.

Cancer treatment had wiped out her white blood cells, and the infection cleared up only after her immune system recovered.

"These findings detail a 'perfect storm' for development of antibiotic tolerance by bacteria that already pose a clinical challenge," Jason Rosch, Ph.D., assistant member of the St. Jude Department of Infectious Diseases, said in a press release.

Researchers conducted an in-depth DNA sequencing of 22 VRE samples from the patient's infection and were able to link the prolonged infection to a point mutation in the reIA gene of VRE. The mutation activated the stringent response pathway, which bacteria use to survive and tolerate antibiotics, and caused elevated levels of the signaling molecule alarmone.

Increased alarmone can prime bacteria to survive exposure to multiple antibiotics and reIA-mutant VRE tolerate significantly higher doses of antibiotics than the original strain of the infection when grown in slimy colonies known as biofilms, according to researchers.

Bacterial biofilms can grow on catheters, heart valves and other surfaces in the body and are difficult to kill with available antibiotics.

"This mutation has particular clinical significance because the antibiotics involved, linezolid and daptomycin, are the last line of defense against VRE infection," Joshua Wolf, co-author and assistant member of the St. Jude Department of Infectious Diseases, said in a press release.

Researchers used the antibiotic ADEP-4, which works by activating an enzyme to kill persister cells and bacterial biofilm, to kill relA-mutant and non-mutant VRE grown in biofilm in the lab.

"In the future, compounds like ADEP-4 may provide a new approach to resolving persistent infections," Wolf said.

The study was published in mBio.