# Intrinsic modifiers of beta-lactam resistance in nosocomial Enterobacterales

> **NIH NIH K08** · MASSACHUSETTS GENERAL HOSPITAL · 2021 · $199,348

## Abstract

Project Summary / Abstract
Increasing rates of antibiotic resistance in common bacterial pathogens threatens to reverse many
of the gains made in human health over the past century. This proposal details a research plan
designed to understand the basic biology of resistance to beta-lactam antibiotics in an important
group of Gram-negative pathogens, the Enterobacterales.
Aim 1 of this proposal concerns a novel, conserved protein that the candidate has discovered helps
mediate beta-lactam resistance in the Enterobacterales. Through targeted experimentation and
quantitative proteomics, the candidate will discover how this protein functions at the molecular
level. Aim 2A takes a broader focus, seeking to characterize how many mutations are necessary to
impart resistance in an important pathogen of hospitalized patients, Serratia marcescens. This is
important to determine, because if this sort of resistance is difficult to acquire, it may be prudent for
clinicians to use narrower, rather than broader antibiotics. Finally, in Aim 2B, the candidate strives
to identify proteins and pathways necessary for a kind of intrinsic resistance that a group of
Enterobacterales can utilize to become resistant to even the last-line carbapenem group of
beta-lactams. This approach has the potential to identify new antibiotic targets.
The candidate’s background includes training in biochemistry and eukaryotic cell biology, as well
as the clinical practice of infectious diseases. This Mentored Clinical Scientist Research Career
Development Award proposes additional training in genomics, proteomics, and transcriptomics
necessary for an independent career investigating clinically relevant problems in the prokaryotic
cell biology of antibiotic resistance. With the guidance of his co-mentors, the candidate will obtain
this additional training using both formal coursework and hands-on training utilizing the best of the
resources available at the Massachusetts General Hospital, Brigham and Women’s Hospital, and
Harvard Medical School.

## Key facts

- **NIH application ID:** 10104633
- **Project number:** 1K08AI155830-01
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Jacob Eric Lazarus
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $199,348
- **Award type:** 1
- **Project period:** 2020-12-15 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10104633

## Citation

> US National Institutes of Health, RePORTER application 10104633, Intrinsic modifiers of beta-lactam resistance in nosocomial Enterobacterales (1K08AI155830-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10104633. Licensed CC0.

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