Targeting Antibiotic Tolerance, Pathogen by Pathogen

Sylvain Meylan; Ian W Andrews; James J Collins

doi:10.1016/j.cell.2018.01.037

Targeting Antibiotic Tolerance, Pathogen by Pathogen

Cell. 2018 Mar 8;172(6):1228-1238. doi: 10.1016/j.cell.2018.01.037.

Authors

Sylvain Meylan¹, Ian W Andrews², James J Collins³

Affiliations

¹ Department of Biomedicine, Basel University Hospital, Basel, CH-4031, Switzerland; Division of Infectious Diseases and Hospital Epidemiology, Basel University Hospital, Basel, CH-4031, Switzerland; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
² Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA; Institute for Medical Engineering & Science, Department of Biological Engineering, and Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
³ Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA; Institute for Medical Engineering & Science, Department of Biological Engineering, and Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard-MIT Program in Health Sciences and Technology, Cambridge, MA 02139, USA. Electronic address: jimjc@mit.edu.

PMID: 29522744
DOI: 10.1016/j.cell.2018.01.037

Abstract

Antibiotic tolerance, the capacity of genetically susceptible bacteria to survive the lethal effects of antibiotic treatment, plays a critical and underappreciated role in the disease burden of bacterial infections. Here, we take a pathogen-by-pathogen approach to illustrate the clinical significance of antibiotic tolerance and discuss how the physiology of specific pathogens in their infection environments impacts the mechanistic underpinnings of tolerance. We describe how these insights are leading to the development of species-specific therapeutic strategies for targeting antibiotic tolerance and highlight experimental platforms that are enabling us to better understand the complexities of drug-tolerant pathogens in in vivo settings.

Publication types

Research Support, N.I.H., Extramural
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 / classification
Bacteria / drug effects*
Bacterial Infections / drug therapy*
Bacterial Infections / microbiology
Bacterial Physiological Phenomena / drug effects
Biofilms / drug effects
Biofilms / growth & development
Drug Tolerance*
Host-Pathogen Interactions / drug effects
Humans
Species Specificity

Substances

Anti-Bacterial Agents

Grants and funding

U19 AI111276/AI/NIAID NIH HHS/United States