# Inflammatory Organ Injury after Pneumonia-Derived Sepsis

> **NIH NIH R01** · LOUISIANA STATE UNIV A&M COL BATON ROUGE · 2024 · $715,216

## Abstract

SUMMARY
Pneumonia-derived sepsis remains a persistent and pervasive public health problem. Pneumonia and
sepsis are the major causes of Acute Respiratory Distress Syndrome (ARDS). No clinical studies other
than the ARDSnet ventilator trial provided better outcomes for ALI/ARDS. Therefore, an improved
understanding of the pathogenesis of pneumonia-derived sepsis is warranted. Despite the use of newer-
generation antibiotics to control pneumonia, the mortality rate of bacterial pneumonia has increased due
to multidrug-resistant and hypervirulent bacterial strains. Infections due to Enterobacteriaceae present a
public health threat due to the emergence of multidrug-resistant strains and limited available therapeutic
options. The acquisition of carbapenemeses by K. pneumoniae makes the bacteria resistant to all -
lactams. Moreover, there are no effective vaccines available to control carbapenem-resistant K.
pneumoniae (CRKP). Therefore, harnessing the host’s immune system may be a more effective strategy
for combating CRKP and developing novel treatment against this pathogen-induced devastating
diseases. The long-term goal is to understand the mechanism by which Nrf2 activation in the lung is
integrated into successful antibacterial resistance and if it is possible to reduce pulmonary and
extrapulmonary organ injury during CRKP infection through host-targeted therapies. My lab has made
substantial contributions toward understanding protective antibacterial defense against pulmonary
infection and pneumonia-induced sepsis. Bacterial pneumonia induces extensive oxidative stress in
pulmonary tissues. The transcription factor Nrf2 (nuclear factor-erythroid 2 p45-related factor 2, Nfe2l2) is
a critical regulator of the expression of oxidative stress genes. The central hypothesis that Nrf2 is a
master regulator of host defense during CRKP-induced infection. Four aims have been proposed: Aim 1
will investigate the effects of Nrf2 on survival, bacterial clearance and neutrophil accumulation and
function, Aim 2 will explore the role of Nrf2 in emergency granulopoiesis, Aim 3 will characterize if Nrf2
ablation can alter the function of alveolar macrophages, and Aim 4 will determine if enhancing Nrf2
signaling in the lungs improve host defense. We will use both in vivo (mouse model) and in vitro (human
cells) strategies. We anticipate gaining a better understanding of the signaling cascades involved in the
innate responses to CRKP infection to design improved therapies to augment host defense and mitigate
collateral tissue damage.

## Key facts

- **NIH application ID:** 10981930
- **Project number:** 1R01AI180123-01A1
- **Recipient organization:** LOUISIANA STATE UNIV A&M COL BATON ROUGE
- **Principal Investigator:** Samithamby Jeyaseelan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $715,216
- **Award type:** 1
- **Project period:** 2024-07-01 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10981930

## Citation

> US National Institutes of Health, RePORTER application 10981930, Inflammatory Organ Injury after Pneumonia-Derived Sepsis (1R01AI180123-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10981930. Licensed CC0.

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