Antibiotic tolerance study paves way for new treatments
Posted on Mar 02, 2021, 3 p.m.
A new study identifies a mechanism that makes bacteria tolerant to penicillin and related antibiotics, findings that could lead to new therapies that boost the effectiveness of these treatments.
Antibiotic tolerance is the ability of bacteria to survive exposure to antibiotics, in contrast to antibiotic resistance, when bacteria actually grow in the presence of antibiotics. Tolerant bacteria can lead to infections that persist after treatment and may develop into resistance over time.
The study in mice, “A Multifaceted Cellular Damage Repair and Prevention Pathway Promotes High Level Tolerance to Beta-lactam Antibiotics,” published Feb. 3 in the journal EMBO Reports, reveals how tolerance occurs, thanks to a system that mitigates iron toxicity in bacteria that have been exposed to penicillin.
Co-authors included Ilana Brito, the Mong Family Sesquicentennial Faculty Scholar and assistant professor in the Meinig School of Biomedical Engineering in the College of Engineering, and Lars Westblade, associate professor of pathology and laboratory medicine at Weill Cornell Medicine.
In the study, the researchers developed a V. cholerae mutant that lacked a two-component damage repair response system that controls a gene network encoding diverse functions. Without the system, known as VxrAB, when the cell wall is damaged by antibiotics, the transfer of electrons across the cell membrane goes awry, leading to electrons ending up on the wrong molecules. This misdirection causes hydrogen peroxide to accumulate in the cell, which changes the oxidation state of cellular iron and disrupts signals for the cell to tell how much iron it has.
Fortunately for normal V. cholerae, exposure to antibiotics and the breakdown of the cell’s walls activate the VxrAB system, which works to repair cell walls and downregulates iron uptake systems, and thereby creates antibiotic tolerance. More study is needed to understand what triggers the VxrAB system in the presence of beta-lactam antibiotics.
Jung-Ho Shin, a postdoctoral researcher in Dörr’s lab, is the paper’s first author. Co-authors include researchers from the Korea Advanced Institute of Science and Technology, the Korea Advanced Institute of Science and Technology, and the Intelligent Synthetic Biology Center in Korea.
The study was funded by the National Research Foundation of Korea and the National Institutes of Health.
https://www.worldhealth.net/news/antibiotic-tolerance-study-paves-way-new-treatments/
