Network Biology Approaches to Bacterial...

Network Biology Approaches to

Bacterial Infections

James J. Collins

Howard Hughes Medical Institute

Dept of Biomedical Engineering & Center of Synthetic Biology

Boston University

Wyss Institute for Biologically Inspired Engineering

Harvard University

Microbial Network Biology and Antibiotic Research

Focus: use network biology approaches to study the actions of

antibiotics and mechanisms underlying the emergence of resistance

Goal: utilize insights gained from these studies to enhance our

existing antibiotic arsenal and treat resistant bacterial infections

Bacterial Persisters: Chronic and Recurrent Infections

Metabolite-Enabled Eradication of Bacterial Persisters

KR Allison et al., Nature, 2011

Metabolic Screen to Potentiate Aminoglycosides

KR Allison et al., Nature, 2011

Metabolic Screen to Potentiate Aminoglycosides

KR Allison et al., Nature, 2011

Metabolite-Enabled Aminoglycoside Uptake

KR Allison et al., Nature, 2011

Metabolite-Enabled Aminoglycoside Uptake and Killing Require PMF

KR Allison et al., Nature, 2011

aminoglycoside uptake and persister

eradication require PMF

Electron Transport Chain is Important to Persister Eradication

KR Allison et al., Nature, 2011

Metabolite-Enabled Eradication of Bacterial Persisters

KR Allison et al., Nature, 2011

Metabolite-Enabled Treatment of Bacterial Biofilms

KR Allison et al., Nature, 2011

Metabolite-Enabled Treatment of Catheter-Associated UTI

KR Allison et al., Nature, 2011

Engineered Bacteriophage as Antibacterial Adjuvants

TK Lu and JJ Collins, PNAS, 2009

Synthetic Probiotics for Detecting and Treating Infections

Lactobacillus

Functionalize the Microbiome Using Engineered Bacteriophage