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Structural Investigations of Biofilm Matrices for Novel Antibiofilm Strategies

Award Number: R01GM123283
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/15/2017
PERIOD OF PERFORMANCE END DATE: 11/30/2024

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Structural Investigations of Biofilm Matrices for Novel Antibiofilm Strategies - Project Summary/Abstract This project will combine molecular dynamics simulations and other types of molecular mechanics calculations with various experimental methods to characterize the biofilms formed by opportunistic pathogen species belonging to the Burkholderia cepacia Complex (BCC) and by Klebsiella pneumoniae. Bacterial biofilms constitute a serious concern in infections since they confer increased resistance towards antimicrobial therapies. In biofilms, bacteria live within a hydrated matrix composed of various macromolecules, and in particular polysaccharides, which are primarily responsible for its formation. Understanding the details of biofilm matrix structure can be of significant utility in designing novel strategies for treating infections. This is the main objective of this proposal, which is a request for the continuation of a currently funded NIH study (GM123283) based on the results acquired in this current project characterizing the structure of polysaccharides produced by species of the BCC and K. pneumoniae. These polymers contain clusters of non-polar rhamnose residues that confer a less polar character to the chains, suggesting the possible formation of hydrophobic juncture zones in the gel- like structures of their biofilm matrices, and possibly constituting targets for biofilm disruption. On the basis of the results already achieved, the following research lines will be explored both experimentally and by computer modelling: 1) Structurally different rhamnose-rich polysaccharides produced by Burkholderia and Klebsiella will be studied to investigate their morphology and aggregation tendency, with the objective of modeling their biofilm matrix architectures. 2) The interactions of matrix polysaccharides with molecules participating in quorum sensing systems will be studied to define the role of the matrix in cell-cell communication. 3) The possibility of weakening matrix architecture by using specific agents will be explored using three systems, all designed to target matrix junction zones: i) oligosaccharides containing rhamnose residues; ii) specific peptides which have already been found, by means of phage display procedures, to bind bacterial polysaccharides; iii) synthetic glycopeptides obtained binding rhamnose residues to selected peptides investigated in point ii). Changes in biofilm matrix morphologies will be studied by adding these test molecules to bacterial cultures.


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 = $0 )
2025	2023	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Biomedical Research and Research Training	000	6	4/16/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $294,400 )
2023	2023	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Biomedical Research and Research Training	001	6	2/16/2023	NON-COMPETING CONTINUATION	$29,440
2023	2023	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Biomedical Research and Research Training	000	6	11/18/2022	NON-COMPETING CONTINUATION	$264,960
														Subtotal = $294,400

Issue Date FY: 2022 ( Subtotal = $315,847 )
2022	2022	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Biomedical Research and Research Training	000	5	11/18/2021	NON-COMPETING CONTINUATION	$284,262
2022	2022	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Biomedical Research and Research Training	001	5	6/27/2022	NON-COMPETING CONTINUATION	$31,585
														Subtotal = $315,847

Issue Date FY: 2021 ( Subtotal = $325,211 )
2021	2021	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Biomedical Research and Research Training	001	4	12/29/2020	COMPETING CONTINUATION	$325,211
2021	2021	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Biomedical Research and Research Training	003	4	7/11/2021	COMPETING CONTINUATION	$8,692
2021	2019	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Biomedical Research and Research Training	002	3	7/11/2021	NON-COMPETING CONTINUATION	-$8,692
2021	2019	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Biomedical Research and Research Training	000	3	12/21/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $325,211

Issue Date FY: 2019 ( Subtotal = $268,447 )
2019	2019	CORNELL UNIVERSITY, INC	373 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Biomedical Research and Research Training	000	3	8/26/2019	NON-COMPETING CONTINUATION	$268,447
														Subtotal = $268,447

Issue Date FY: 2018 ( Subtotal = $253,588 )
2018	2018	CORNELL UNIVERSITY, INC	373 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Biomedical Research and Research Training	001	2	8/31/2018	NON-COMPETING CONTINUATION	$264,338
2018	2017	CORNELL UNIVERSITY, INC	373 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Biomedical Research and Research Training	000	1	11/9/2017	NEW	-$10,750
														Subtotal = $253,588

Issue Date FY: 2017 ( Subtotal = $287,009 )
2017	2017	CORNELL UNIVERSITY, INC	373 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Biomedical Research and Research Training	000	1	9/11/2017	NEW	$287,009
														Subtotal = $287,009

Grand Total All Awards = $1,744,502

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Structural Investigations of Biofilm Matrices for Novel Antibiofilm Strategies

Award Number: R01GM123283

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/15/2017

PERIOD OF PERFORMANCE END DATE: 11/30/2024

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