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Refining our understanding of antimicrobial peptide mediated disruption of the Klebsiella pneumoniae capsule

Award Number: R00AI163295
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/24/2021
PERIOD OF PERFORMANCE END DATE: 03/31/2026

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Refining our understanding of antimicrobial peptide mediated disruption of the Klebsiella pneumoniae capsule - Project Summary Multi-drug resistant Klebsiella pneumoniae bacterial infections are a major threat to human health as mortality rates are steadily on the rise. One of the defining characteristics of K. pneumoniae is a robust capsule that aids in resistance to the human complement system, host antimicrobial peptides, and last resort therapeutic polymyxins. However, there have not been significant efforts to identify the attributes that allow active peptides to bypass the capsule of K. pneumoniae. I have previously discovered a novel mechanism of peptide disruption of the capsule barrier of K. pneumoniae. I hypothesize there are amino acid residues that change the physiochemical attributes and allow for penetration through the capsule. During the K99 phase of this proposal I will: 1) Define how host defense peptides fit into the novel mechanism of capsule disruption; and 2) Identify broader set of physiochemical characteristics that allow for disruption of the K. pneumoniae capsule. The objective of these aims is to determine how well studied host defense peptides fit into the mechanism of capsule disruption using biochemical and biophysical experiments and determine the physiochemical attributes that allow for peptide aggregation and disruption of K. pneumoniae capsule. The R00 phase will build on the K99 phase, to identify the structural components of bacterial capsule that is aggregating with peptides and reveal the implications of therapeutic capsule removal on the infection process of K. pneumoniae using peptides discovered in the K99 phase. The K99/R00 award will allow me to utilize the extensive resources available at the University of Texas at Austin while working with my mentor team to ensure successful transition to an independent research position. The results of the studies completed in this award will provide a greater understanding of peptide disruption of capsule and how this changes the infection process of K. pneumoniae.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $249,000 )
2025	2025	THE UNIVERSITY OF CENTRAL FLORIDA BOARD OF TRUSTEES	4000 CENTRAL FLORIDA BLVD	ORLANDO	FL	32816	ORANGE	USA	Allergy and Infectious Diseases Research	000	5	4/10/2025	NON-COMPETING CONTINUATION	$249,000
														Subtotal = $249,000

Issue Date FY: 2024 ( Subtotal = $249,000 )
2024	2024	THE UNIVERSITY OF CENTRAL FLORIDA BOARD OF TRUSTEES	4000 CENTRAL FLORIDA BLVD	ORLANDO	FL	32816	ORANGE	USA	Allergy and Infectious Diseases Research	000	4	3/12/2024	NON-COMPETING CONTINUATION	$249,000
2024	2024	THE UNIVERSITY OF CENTRAL FLORIDA BOARD OF TRUSTEES	4000 CENTRAL FLORIDA BLVD	ORLANDO	FL	32816	ORANGE	USA	Allergy and Infectious Diseases Research	001	4	3/13/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $249,000

Issue Date FY: 2023 ( Subtotal = $315,131 )
2023	2023	THE UNIVERSITY OF CENTRAL FLORIDA BOARD OF TRUSTEES	4000 CENTRAL FLORIDA BLVD	ORLANDO	FL	32816	ORANGE	USA	Allergy and Infectious Diseases Research	001	3	9/19/2023	EXTENSION WITH OR WITHOUT FUNDS	$66,131
2023	2023	UNIVERSITY OF CENTRAL FLORIDA BOARD OF TRUSTEES, THE	4000 CENTRAL FLORIDA BLVD	ORLANDO	FL	32816	ORANGE	USA	Allergy and Infectious Diseases Research	000	3	4/3/2023	EXTENSION WITH OR WITHOUT FUNDS	$249,000
														Subtotal = $315,131

Grand Total All Awards = $813,131

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Refining our understanding of antimicrobial peptide mediated disruption of the Klebsiella pneumoniae capsule

Award Number: R00AI163295

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/24/2021

PERIOD OF PERFORMANCE END DATE: 03/31/2026

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