About

Kim Lewis is a professor affiliated with the Bioengineering department at Northeastern University College of Engineering. His research focuses on antimicrobial drug tolerance and antibiotic discovery. He investigates how microorganisms produce persister cells, which are dormant variants highly tolerant to antibiotics and largely responsible for relapsing chronic infections caused by biofilms. Using techniques such as transcriptome analysis, cell sorting, and whole genome sequencing, he aims to identify genes responsible for persister formation. His work includes screening compounds from previously uncultured microbial species and high-throughput screening for compounds with novel modes of action. Lewis holds a Ph.D. in Biochemistry and a B.Sc. in Biology from Moscow University, Moscow, USSR. His contributions to the field include identifying mechanisms of drug tolerance, discovering new antibiotics, and advancing microbiome therapeutics.

Research topics

• Biology
• Biochemistry
• Biophysics
• Microbiology
• Genetics
• Pathology
• Immunology
• Computational biology
• Intensive care medicine
• Chemistry
• Cell biology
• Stereochemistry
• Medicine

Selected publications

• Teixobactin kills bacteria by a two-pronged attack on the cell envelope

  Nature · 2022 · 189 citations

  • Chemistry
  • Biophysics
  • Biochemistry

  . The supramolecular structure compromises membrane integrity. Atomic force microscopy and molecular dynamics simulations show that the supramolecular structure displaces phospholipids, thinning the membrane. The long hydrophobic tails of lipid II concentrated within the supramolecular structure apparently contribute to membrane disruption. Teixobactin hijacks lipid II to help destroy the membrane. Known membrane-acting antibiotics also damage human cells, producing undesirable side effects. Teixobactin damages only membranes that contain lipid II, which is absent in eukaryotes, elegantly resolving the toxicity problem. The two-pronged action against cell wall synthesis and cytoplasmic membrane produces a highly effective compound targeting the bacterial cell envelope. Structural knowledge of the mechanism of teixobactin will enable the rational design of improved drug candidates.

  DOI

• Bacterial persisters are a stochastically formed subpopulation of low-energy cells

  PLoS Biology · 2021 · 166 citations

  Senior authorCorresponding
  • Biology
  • Microbiology
  • Cell biology

  Persisters represent a small subpopulation of non- or slow-growing bacterial cells that are tolerant to killing by antibiotics. Despite their prominent role in the recalcitrance of chronic infections to antibiotic therapy, the mechanism of their formation has remained elusive. We show that sorted cells of Escherichia coli with low levels of energy-generating enzymes are better able to survive antibiotic killing. Using microfluidics time-lapse microscopy and a fluorescent reporter for in vivo ATP measurements, we find that a subpopulation of cells with a low level of ATP survives killing by ampicillin. We propose that these low ATP cells are formed stochastically as a result of fluctuations in the abundance of energy-generating components. These findings point to a general "low energy" mechanism of persister formation.

  DOI

• Recent Progress in Lyme Disease and Remaining Challenges

  Frontiers in Medicine · 2021 · 150 citations

  • Medicine
  • Intensive care medicine
  • Immunology

  Lyme disease (also known as Lyme borreliosis) is the most common vector-borne disease in the United States with an estimated 476,000 cases per year. While historically, the long-term impact of Lyme disease on patients has been controversial, mounting evidence supports the idea that a substantial number of patients experience persistent symptoms following treatment. The research community has largely lacked the necessary funding to properly advance the scientific and clinical understanding of the disease, or to develop and evaluate innovative approaches for prevention, diagnosis, and treatment. Given the many outstanding questions raised into the diagnosis, clinical presentation and treatment of Lyme disease, and the underlying molecular mechanisms that trigger persistent disease, there is an urgent need for more support. This review article summarizes progress over the past 5 years in our understanding of Lyme and tick-borne diseases in the United States and highlights remaining challenges.

  DOI

• The Science of Antibiotic Discovery

  Cell · 2020 · 765 citations

  1st authorCorresponding
  • Biology
  • Computational biology
  • Microbiology
  DOI

Recent grants

• NIH Grant R01GM059903

  NIH · $237k · 2003

• NIH Grant R21AI059483

  NIH · $629k · 2007

• A GENOMICS APPROACH TO DRUG TOLERANCE

  NIH · $4.2M · 2000–2012

• Super-persistent cells and the paradox of untreatable infections

  NIH · $5.2M · 2009–2015

• Admin Core

  NIH · $17.8M · 2016–2023

Frequent coauthors

• Lawrence Mulcahy

  Ernst & Young (United States)

  30 shared

• Frank R. Stermitz

  Colorado State University

  19 shared

• Amy L. Spoering

  NovoBiotic Pharmaceuticals

  19 shared

• Anthony D’Onofrio

  Merck & Co., Inc., Rahway, NJ, USA (United States)

  13 shared

• Losee L. Ling

  NovoBiotic Pharmaceuticals

  13 shared

• George P. Tegos

  Drexel University

  12 shared

• Brian P. Conlon

  University of North Carolina at Chapel Hill

  12 shared

• Sonja Hansen

  12 shared

Awards & honors

• Stanford University Annual Assessment of Author Citations (2…

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• Herbert Levineh-119
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