# Assessing Klebsiella pneumoniae invasion of the intact gut microbiome

> **NIH NIH K99** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $59,049

## Abstract

Project summary/abstract
The bacteria Klebsiella pneumoniae is an important cause of hospital-acquired and antibiotic-resistant infections,
including pneumonia, bacteremia, and urinary tract infection. Infection risk sharply increases when K.
pneumoniae is present in the gut, and K. pneumoniae must overcome many barriers to successfully colonize the
gut, including the gut microbiome. While disruption of the gut microbiome through antibiotics can permit
colonization, K. pneumoniae frequently colonizes the gut in the absence of antibiotics when an intact microbiome
is present. There is a fundamental gap in our understanding of how K. pneumoniae invades the intact gut
microbiome. Furthermore, the specific mechanisms underlying the ability of K. pneumoniae to compete with the
endogenous gut microbiota remain unexplored. The objective of this proposal is to identify and characterize
factors necessary for K. pneumoniae gut colonization in an intact gut microbiome and determine how these
factors influence K. pneumoniae fitness in the gut. The central hypothesis of this proposal is that Kp employs
microbiome dependent and specific factors to enhance their ability to directly compete with the host microbiota
or survive microbiota-mediated modulation of host inflammation to invade the intact gut microbiome, which is
critical for Kp gut colonization. I will test this hypothesis in three specific aims: 1) define the role of a previously
identified gut fitness factor, the tellurium resistance (ter) operon during invasion of an intact gut microbiome; 2)
determine the role of the ter operon in response to physiologically relevant stresses and; 3) systematically identify
K. pneumoniae fitness factors during invasion of intact gut microbiomes. The work in this proposal is innovative,
as it requires the development of novel transposon sequencing application, and it addresses a gap in
understanding that can shift the current paradigm of K. pneumoniae gut colonization. Completion of this work
will have sustained positive impact through the identification, characterization, and prioritization of K.
pneumoniae factors necessary for invasion of the intact gut microbiome, which will help guide the development
of therapeutics targeted at the disruption of K. pneumoniae gut colonization. Finally, the research in this proposal
is complemented by a comprehensive training plan designed to develop a foundational skillset for the pursuit of
research focused on mechanisms of bacterial pathogenesis directly informed by and applicable to the clinic. This
project will be undertaken within the University of Michigan in conjunction with a distinguished team of co-
mentors. This team of co-mentors will complement that candidate's expertise in host-pathogen interaction by
providing training in microbial ecology, exploration of bacterial physiology, and comprehensive analyses of host-
microbial systems necessary for the candidate's transition to independence. These state-of-the-art stu...

## Key facts

- **NIH application ID:** 10462499
- **Project number:** 5K99AI153483-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Jay Vornhagen
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $59,049
- **Award type:** 5
- **Project period:** 2021-08-05 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10462499

## Citation

> US National Institutes of Health, RePORTER application 10462499, Assessing Klebsiella pneumoniae invasion of the intact gut microbiome (5K99AI153483-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10462499. Licensed CC0.

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