# Elucidating physiology of dormant bacteria to combat antibiotic persistence

> **NIH NIH R35** · HARVARD MEDICAL SCHOOL · 2024 · $215,562

## Abstract

Project Summary
Most antibiotics are ineffective for killing dormant bacteria and it is estimated that 50% of antibiotic
tolerance cases are due to phenotypic ‘persistence’ rather than genetic resistance: bacteria can
survive drug treatment simply because a few of them are metabolically dormant. For example,
nutrient and oxygen depletion in the center of biofilms renders bacteria metabolically dormant and
antibiotic tolerant. Once the antibiotic is withdrawn, recurrence gives bacteria the chance to evolve
antibiotic resistance. Common examples of recurrent infections include urinary tract infections of
pathogenic E. coli—the most common bacterial infection in women in developed countries—latent
tuberculosis, and biofilm-forming bacteria, like the P. aeruginosa infections that often complicate
wound healing and commonly affect cystic fibrosis patients. To develop new strategies to combat
recurring infections and persistence, we need a better understanding of dormant bacteria.
My laboratory aims to identify new antibiotic targets that are effective against dormant bacteria. By
studying spontaneous death rates of dormant bacteria, we have already identified key vulnerabilities.
We found that death rates of dormant bacteria critically depend on previous growth conditions. By
correlating proteomics data with death rates, we have identified hundreds of genes that may
contribute to survival and adaptation processes of dormant bacteria. We have validated many of our
candidates using genetics, and discovered a crucial role of the bacterial outer membrane for the
survival of dormant bacteria. We now need to uncover how the outer membrane mechanistically
contributes to survival during dormancy and understand a complex interplay between the cell
envelope, osmoregulation and energy metabolism that we have discovered. A better understanding of
these processes will reveal the most promising antibiotic targets and effective combinations of
existing drugs against dormant bacteria. My lab's interdisciplinary experience in quantitative biology
and biophysics puts us in a unique position to answer these questions and to provide key insights into
the physiology of dormant states.

## Key facts

- **NIH application ID:** 11037118
- **Project number:** 3R35GM137895-04S1
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Markus Thomas Basan
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $215,562
- **Award type:** 3
- **Project period:** 2020-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11037118

## Citation

> US National Institutes of Health, RePORTER application 11037118, Elucidating physiology of dormant bacteria to combat antibiotic persistence (3R35GM137895-04S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/11037118. Licensed CC0.

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