# The SOS Response as a Generator of Antibiotic Resistance and Role of Zinc as SOS Inhibitor

> **NIH NIH R21** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2020 · $199,375

## Abstract

Project Abstract/Summary.
 Bacteria, like human beings, often find themselves under stressful circumstances. Bacterial
cells, like other living organisms, have evolved stress response pathways to cope with adverse
conditions. One of these stress response pathways, called the SOS response, is triggered by DNA
damage in bacterial cells. Among other things, the SOS response triggers the expression of alternate
DNA polymerases which can repair DNA that has been severely damaged, for example by
ultraviolet (UV) light, environmental chemicals, or antibiotics. Repair of damaged DNA, called
trans-lesion synthesis, forces the bacteria to use error-prone DNA polymerases, such as DNA
polymerases IV and V. As a result, the SOS response triggers an increase in the mutation rate
observed in bacteria. The SOS response triggers a strong increase in the rate at which bacteria
acquire resistance to antibiotics, as well as mutations in other genes. Zinc blocks the SOS response
in bacteria, and prevents the increase in mutation rate, which is also called the mutator response, or
hypermutation. Zinc blocks hypermutation by preventing a key bacterial protein, RecA, from
binding to single-stranded DNA. RecA is the molecule that serves as the sensor of DNA damage in
E. coli and in other bacteria, and which triggers the onset of the SOS response.
 In addition to triggering an increase in the rate of acquisition of antibiotic resistance within a
bacterial strain, our laboratory has recently shown that the SOS response can trigger the transfer of
an antibiotic resistance gene between species. Zinc also blocked this horizontal transfer of DNA
from Enterobacter cloacae to E. coli.
 This grant application proposes experiments to complete our understanding of how zinc
blocks the function of RecA, and thereby blocks hypermutation as well. The additive or synergistic
interaction between zinc and nitric oxide donors will also be explored. In addition, experiments will
be conducted in vivo in rabbit intestine to quantitate how much the SOS response contributes to
hypermutation, and if it can be blocked by zinc in the gut. The intestinal tract, with its rich
microbiome, is often the anatomic site in which antibiotic resistance elements are exchanged among
microbes.
 Currently, our country and world are in the middle of an antibiotic resistance crisis.
Understanding the protective effects of zinc could allow us to preserve the remaining antibiotics
that are still active against multi-drug resistant bacterial pathogens, and could be used to prevent
emergence of resistance against new antibiotics that might be developed in the future.

## Key facts

- **NIH application ID:** 9936364
- **Project number:** 5R21AI145836-02
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** John K. Crane
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $199,375
- **Award type:** 5
- **Project period:** 2019-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9936364

## Citation

> US National Institutes of Health, RePORTER application 9936364, The SOS Response as a Generator of Antibiotic Resistance and Role of Zinc as SOS Inhibitor (5R21AI145836-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9936364. Licensed CC0.

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