# Klebsiella pneumoniae pathogenesis in the obese lung

> **NIH NIH R03** · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · 2021 · $78,000

## Abstract

Obesity is a major public health issue and the obese population is steadily increasing. One consequence
of obesity is increased susceptibility to bacterial pneumonia. While altered immune function in the lung is an
important driver of this susceptibility, the contribution of the bacterial response to the obese lung environment
has not been examined. Klebsiella pneumoniae (Kp) is one of the bacteria to which obese individuals are
susceptible and is an important drug-resistant pathogen. The goal of this proposal is to examine the bacterial
response to the obese lung and use this to better understand host biology and bacterial pathogenesis during
infection. Our published preliminary data show increased susceptibility of obese mice to Kp using four
different mouse models, three genetic (db/db, ob/ob, and CPEfat/fat) and one high-fat diet-induced (DIO).
While all four obese models are more susceptible to Kp than lean littermates, each shows different bacterial
growth/survival kinetics in the lung. Each model manifests different degrees of diabetes and other elements
of the metabolic syndrome meaning that interaction of the bacteria with each of these models happens in an
environment that is likely chemically and immunologically different. Our preliminary data of Kp transcriptome
response to db/db bronchoalveolar lavage fluid combined with our published data on host cellular immune
defects suggests that host defects are combined with pro-pathogenic bacterial responses to the obese lung
environment to promote infection in the lung. The bacterial response in these four obese models will be used
to identify Kp genes important for infection of obese mice as well as provide a means to probe altered host
physiology, via two Specific Aims: (1) Use the Kp transcriptome response to identify genes contributing to
infection in obesity models and (2) Use Kp transcriptomes to identify altered host parameters in the lung.
Complete Kp transcriptomes from the four obese models will allow specific dissection of the host-pathogen
interface related to obesity, and using Kp as a living probe will uncover altered airspace lining fluid
composition in obesity that will vary with the elements and degree of metabolic syndrome expression in each
model. The bulk of bacterial-host interaction studies in obesity have focused on deficiencies in the host
cellular immune response. Here we will use the transcriptome response of Kp to understand changes to the
lung airspace during obesity that alter bacterial gene expression. The ability to compare and test mutant
phenotypes in relation to four different models of obesity will allow discovery of new aspects of host-bacterial
interactions, and provide a foundation for mechanistic understanding of these interactions.

## Key facts

- **NIH application ID:** 10149242
- **Project number:** 5R03AI151525-02
- **Recipient organization:** UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
- **Principal Investigator:** MATTHEW J WARGO
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $78,000
- **Award type:** 5
- **Project period:** 2020-04-21 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10149242

## Citation

> US National Institutes of Health, RePORTER application 10149242, Klebsiella pneumoniae pathogenesis in the obese lung (5R03AI151525-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10149242. Licensed CC0.

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