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Comparative structural and functional analysis of Pseudomonas aeruginosa inhibitor of vertebrate lysozyme paralogs

Award Number: R16AI167815
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary – Comparative structural and functional analysis of Pseudomonas aeruginosa inhibitor of vertebrate lysozyme paralogs. Thomas Leeper, PI, Kennesaw State University. The proposed integrative studies will investigate a significant regulator of peptidoglycan biochemistry in the cystic fibrosis pathogen Pseudomonas aeruginosa (PA), known to display multidrug resistance (MDR). Specifically, Inhibitor of Vertebrate Lysozyme protein 2 (IVYp2) will have its structure determined by NMR (Aim 1) and compared to its ability to inhibit hydrolase enzyme kinetics (Aim 2). While IVY proteins were originally suggested to inhibit lysozyme glycoside hydrolases, subsequent work suggested that the evolutionary origin of IVY’s may have been to inhibit lytic transglycosylases (LTs). For example, IVYp2 has no effect on lysozyme activity in enzyme inhibition assays but has been shown to inhibit LTs, at least in vitro. In order to determine which LTs are recognized in vivo enzyme inhibition assays with LTs (Aim 2) will be compared to novel applications of complementation and genetically encoded crosslinking studies in IVY knockout PA strains (Aim 3). The identified cognate IVY-LT pairs will be compared to the NMR structure of IVYp2 (Aim 1) and existing complex structures for other IVYs (i.e. IVYp1) bound to lysozyme to suggest regions important for LT molecular recognition. Graduate and undergraduate students, particularly those from underrepresented groups, will significantly participate in this research to facilitate data collection while providing them important training and advancement opportunities. These innovative studies will establish the background and workflow needed for future drug discovery efforts to develop new drug classes targeting novel biochemical pathways in MDR PA.


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: 2024 ( Subtotal = $135,500 )
2024	2024	KENNESAW STATE UNIVERSITY	1000 CHASTAIN RD NW	KENNESAW	GA	30144	COBB	USA	Allergy and Infectious Diseases Research	000	3	8/7/2024	NON-COMPETING CONTINUATION	$135,500
														Subtotal = $135,500

Issue Date FY: 2023 ( Subtotal = $135,500 )
2023	2023	KENNESAW STATE UNIVERSITY	1000 CHASTAIN RD	KENNESAW	GA	30144	COBB	USA	Allergy and Infectious Diseases Research	000	2	6/27/2023	NON-COMPETING CONTINUATION	$135,500
														Subtotal = $135,500

Issue Date FY: 2022 ( Subtotal = $135,500 )
2022	2022	KENNESAW STATE UNIVERSITY	1000 CHASTAIN RD	KENNESAW	GA	30144	COBB	USA	Allergy and Infectious Diseases Research	000	1	8/26/2022	NEW	$135,500
														Subtotal = $135,500

Grand Total All Awards = $406,500

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Comparative structural and functional analysis of Pseudomonas aeruginosa inhibitor of vertebrate lysozyme paralogs

Award Number: R16AI167815

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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