RT Journal Article
SR Electronic
T1 Tradeoffs in bacterial physiology determine the efficiency of antibiotic killing
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.03.09.483592
DO 10.1101/2022.03.09.483592
A1 Bren, Anat
A1 Glass, David S.
A1 Kohanim, Yael Korem
A1 Mayo, Avi
A1 Alon, Uri
YR 2022
UL http://biorxiv.org/content/early/2022/11/29/2022.03.09.483592.abstract
AB Antibiotics can kill or stop the growth of bacteria, and their effectiveness depends on many factors. It is important to understand the relation between bacterial physiology, the environment and antibiotic action. While many of the mechanistic details of antibiotic action are known, the connection between death rate and bacterial physiology is poorly understood. Death rate in antibiotics has often been shown to rise linearly with growth rate; however, it remains unclear how environmental factors, in concert with whole-cell physiological properties, affect bactericidal activity. To address this, we developed a high-throughput assay to precisely measure antibiotic-mediated bacterial death. We found that death rate is linear in growth rate, but the slope depends on environmental conditions. Specifically, stressors lower the death rate compared to a non-stressed environment with the same growth rate. To understand the role of stress, we developed a mathematical model of bacterial death based on resource allocation that takes into account a newly defined stress-response sector; we identify this sector using RNA-seq. Our model accurately predicts the death rate and minimal inhibitory concentration of antibiotics across a wide range of conditions, including a previously unknown increase in the stress response and protection from death at very low levels of cAMP. The present death-growth model suggests conditions that may improve antibiotic efficacy.Competing Interest StatementThe authors have declared no competing interest.