Bacterial Metabolism and Antibiotic Efficacy

Jonathan M Stokes; Allison J Lopatkin; Michael A Lobritz; James J Collins

doi:10.1016/j.cmet.2019.06.009

Bacterial Metabolism and Antibiotic Efficacy

Cell Metab. 2019 Aug 6;30(2):251-259. doi: 10.1016/j.cmet.2019.06.009. Epub 2019 Jul 3.

Authors

Jonathan M Stokes¹, Allison J Lopatkin², Michael A Lobritz³, James J Collins⁴

Affiliations

¹ Institute for Medical Engineering & Science, Department of Biological Engineering, and Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Infectious Disease & Microbiome Program, Broad Institute of MIT & Harvard, Cambridge, MA 02142, USA; Machine Learning for Pharmaceutical Discovery and Synthesis Consortium, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
² Institute for Medical Engineering & Science, Department of Biological Engineering, and Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Infectious Disease & Microbiome Program, Broad Institute of MIT & Harvard, Cambridge, MA 02142, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
³ Roche Pharma Research and Early Development, Roche Innovation Center Basel, 4070 Basel, Switzerland.
⁴ Institute for Medical Engineering & Science, Department of Biological Engineering, and Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Infectious Disease & Microbiome Program, Broad Institute of MIT & Harvard, Cambridge, MA 02142, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA; Harvard-MIT Program in Health Sciences and Technology, Cambridge, MA 02139, USA. Electronic address: [email protected].

Abstract

Antibiotics target energy-consuming processes. As such, perturbations to bacterial metabolic homeostasis are significant consequences of treatment. Here, we describe three postulates that collectively define antibiotic efficacy in the context of bacterial metabolism: (1) antibiotics alter the metabolic state of bacteria, which contributes to the resulting death or stasis; (2) the metabolic state of bacteria influences their susceptibility to antibiotics; and (3) antibiotic efficacy can be enhanced by altering the metabolic state of bacteria. Altogether, we aim to emphasize the close relationship between bacterial metabolism and antibiotic efficacy as well as propose areas of exploration to develop novel antibiotics that optimally exploit bacterial metabolic networks.

Keywords: antibiotic adjuvants; antibiotic mechanism; antibiotic tolerance; bacterial metabolism.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Review

MeSH terms

Animals
Anti-Bacterial Agents / pharmacology*
Bacteria / drug effects*
Bacteria / metabolism*
Humans
Microbial Sensitivity Tests

Substances

Anti-Bacterial Agents