# Elucidating physiology of dormant bacteria to combat antibiotic persistence

> **NIH NIH R35** · HARVARD MEDICAL SCHOOL · 2022 · $419,863

## Abstract

APPLICATION TITLE
Elucidating physiology of dormant bacteria to combat antibiotic persistence
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 Once the antibiotic is withdrawn, recurrence gives bacteria the chance to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:** 10466963
- **Project number:** 5R35GM137895-03
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Markus Thomas Basan
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $419,863
- **Award type:** 5
- **Project period:** 2020-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10466963

## Citation

> US National Institutes of Health, RePORTER application 10466963, Elucidating physiology of dormant bacteria to combat antibiotic persistence (5R35GM137895-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10466963. Licensed CC0.

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