# Innate Immune Clearance of Host-Adapted Pulmonary Pathogens

> **NIH NIH R35** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $861,202

## Abstract

Abstract
Pneumonia caused by host-adapted, multiple drug resistant bacterial pathogens is a major clinical
problem, associated with both primary infections and complications of hospitalization. Much of the
pathology associated with these pathogens is due to the host response that is elicited ; either excessive
inflammation that causes respiratory failure or an immunosuppressive response that permits
unimpeded bacterial replication, pulmonary damage and sepsis. Organisms such as MRSA,
Pseudomonas aeruginosa and Klebsiella pneumoniae readily adapt to the milieu within the human
airways, acquiring mutations that affect their metabolism, immunogenicity as well as their resistance to
antimicrobial agents. The goal of our studies is to apply a comprehensive approach to fully characterize
such host adapted pathogens, isolated from patients, by using whole gen ome sequencing, murine
modeling of immunogenicity, and proteomics. This type of analysis can provide the data necessary to
identify bacterial components associated with specific patterns of infection. Bacterial genes that are
linked to immuno-pathogenicity can be identified in clinical isolates in real time, just as methicillin
resistance genes are routinely screened in staphylococci. A better understanding of the host response
that is elicited will be used to apply immunomodulatory therapy to complement the often ineffective
antimicrobial agents used to treat pneumonia. In other branches of medicine, targeting the
inflammasome, IL-1, T cell signaling and TNF cascades have become standards of care and new immune
targets are under active development. A comprehensive understanding of both the properties of the
infecting organism and the host response that is evoked can be used to develop a strategy of precision
medicine for the treatment of bacterial pneumonia.

## Key facts

- **NIH application ID:** 9836877
- **Project number:** 5R35HL135800-04
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Alice S Prince
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $861,202
- **Award type:** 5
- **Project period:** 2017-01-11 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9836877

## Citation

> US National Institutes of Health, RePORTER application 9836877, Innate Immune Clearance of Host-Adapted Pulmonary Pathogens (5R35HL135800-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9836877. Licensed CC0.

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