# The Role of Enterococcus Unique Hypothetical EF1909 in Intrinsic β-lactam Resistance

> **NIH NIH R21** · MASSACHUSETTS EYE AND EAR INFIRMARY · 2022 · $253,000

## Abstract

Project summary:
Enterococci are leading causes of multidrug resistant hospital acquired infection – the first E in
the ESKAPE acronym. We recently showed that the genus Enterococcus differs from its closest
extant ancestors in having evolved enhanced traits for survival, including to starvation and
desiccation, as well as to challenge by antibiotics and other biocides that target the cell surface.
That is, in diverging from its ancestors hundreds of millions of years ago, it gained features making
the cell more rugged and impermeable. We found that enterococci possess 10 genes that are
rare or do not exist outside of the genus. Moreover, we found that one of these, encoding a
hypothetical protein, contributes to intrinsic resistance to b-lactams – the largest class of
antibiotics used in human medicine. As a result of this intrinsic resistance, this antibiotic class has
been of limited use in controlling enterococcal infection. Here we propose to validate the
preliminary results implicating this gene, termed EF1909, in contributing to intrinsic b-lactam
resistance and more rigorously and fully assess the phenotype of cells engineered to lack this
feature. We additionally assess when in the growth cycle that EF1909 is expressed and determine
whether its presence/absence results in cell wall peptiglycan of altered composition as implicated
by its contribution to intrinsic b-lactam resistance. If we are able to substantiate the preliminary
indications of phenotype in this exploratory work, this would raise the prospect of then screening
for EF1909 inhibitors that would be predicted to render enterococci now vulnerable to inexpensive
and readily available b-lactam antibiotics. Rendering enterococci readily treatable by b-lactams
would be an advance of very high impact for global health.

## Key facts

- **NIH application ID:** 10464409
- **Project number:** 1R21AI169730-01
- **Recipient organization:** MASSACHUSETTS EYE AND EAR INFIRMARY
- **Principal Investigator:** Michael S Gilmore
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $253,000
- **Award type:** 1
- **Project period:** 2022-02-08 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10464409

## Citation

> US National Institutes of Health, RePORTER application 10464409, The Role of Enterococcus Unique Hypothetical EF1909 in Intrinsic β-lactam Resistance (1R21AI169730-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10464409. Licensed CC0.

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