# Intrinsic cephalosporin resistance in enterococci

> **NIH NIH R01** · MEDICAL COLLEGE OF WISCONSIN · 2020 · $385,000

## Abstract

PROJECT SUMMARY
The continued and inevitable emergence of antibiotic resistance demands a vigorous and sustained
effort to identify fundamentally new targets and strategies for innovative antimicrobial therapeutics.
Antibiotic-resistant enterococci are major causes of hospital-acquired infections. Enterococci are
successful hospital-acquired pathogens in part because of their intrinsic resistance to commonly used
antibiotics that target the bacterial cell envelope, such as cephalosporins. However, many questions
remain regarding the genetic and biochemical basis for cephalosporin resistance in enterococci.
Previous work revealed a key role for a transmembrane protein kinase (IreK) and its intracellular
substrate (IreB) in regulation of cephalosporin resistance, but the downstream effectors in the signaling
pathway remain unknown. In preliminary studies we showed that one (MurAA) of two UDP-GlcNAc
1-carboxyvinyltransferases encoded in E. faecalis (catalyzing the first committed step in peptidoglycan
biosynthesis) is specifically required for cephalosporin resistance. The paralog of MurAA (MurAB)
cannot drive cephalosporin resistance. Hence, MurAA possesses a specialized, specific ability to
promote cephalosporin resistance. The major knowledge gaps to be addressed are that (i) a
biochemical link between the IreK pathway and MurAA has not been established, and (ii) the
mechanism by which MurAA drives cephalosporin resistance is unknown. The research proposed here
is designed to elucidate new insights into the role of MurAA in the biological processes that drive
enterococcal cephalosporin resistance. By doing so, we will provide new insights into the fundamental
biological processes that drive key antibiotic resistance in enterococci and may define new targets for
innovative therapeutics designed to impair enterococcal cephalosporin resistance.

## Key facts

- **NIH application ID:** 9993204
- **Project number:** 5R01AI134660-03
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** CHRISTOPHER J KRISTICH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $385,000
- **Award type:** 5
- **Project period:** 2018-09-14 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9993204

## Citation

> US National Institutes of Health, RePORTER application 9993204, Intrinsic cephalosporin resistance in enterococci (5R01AI134660-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9993204. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*