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Novel linear lipopeptide paenipeptins sensitize multidrug-resistant Gram-negative pathogens to antibiotics

Award Number: R21AI146693
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 The Infectious Diseases Society of America recently identified a list of antibiotic-resistant pathogens that can escape the effect of most antimicrobial agents. These problematic pathogens include Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp., which are collectively abbreviated as ESKAPE. Therefore, there is an urgent need to develop effective antibiotics to keep up with antibiotic resistance. Paenipeptins are novel synthetic linear lipopeptides, which are made of 9 amino acid residues and a fatty acyl group at the N-terminus. They showed highly potent activity in combination with clarithromycin against Gram- negative pathogens in vitro. The overall goal of this project is to develop novel linear lipopeptide antibiotic potentiators, which can be co-administered with FDA-approved antibiotics, to expand their antimicrobial spectrum and enhance the antibiotic activity for the treatment of infections associated with polymyxin-resistant and carbapenem-resistant pathogens. To achieve this goal, the following two aims are set. Aim 1: Evaluate the synergistic effect between paenipeptin analogues and clarithromycin in vitro against a large number of carbapenem-resistant clinical isolates and investigate the mechanism of synergism. Aim 2: Develop antimicrobial-loaded hydrogels for localized delivery of paenipeptin-clarithromycin mixture for topical treatment of wound infections.


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: 2022 ( Subtotal = -$4,331 )
2022	2020	UNIVERSITY OF ARKANSAS FOR MEDICAL SCIENCES	4301 W MARKHAM ST	LITTLE ROCK	AR	72205	PULASKI	USA	Allergy and Infectious Diseases Research	000	2	2/28/2022	NON-COMPETING CONTINUATION	-$4,331
														Subtotal = -$4,331

Issue Date FY: 2020 ( Subtotal = $190,000 )
2020	2020	UNIVERSITY OF ARKANSAS SYSTEM	4301 W MARKHAM ST SLOT 812 BIO-MED BLDG 1 STE 102	LITTLE ROCK	AR	72205	PULASKI	USA	Allergy and Infectious Diseases Research	000	2	6/2/2020	NON-COMPETING CONTINUATION	$190,000
														Subtotal = $190,000

Issue Date FY: 2019 ( Subtotal = $226,500 )
2019	2019	UNIVERSITY OF ARKANSAS SYSTEM	4301 W MARKHAM ST SLOT 812 BIO-MED BLDG 1 STE 102	LITTLE ROCK	AR	72205	PULASKI	USA	Allergy and Infectious Diseases Research	000	1	5/27/2019	NEW	$226,500
														Subtotal = $226,500

Grand Total All Awards = $412,169

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Novel linear lipopeptide paenipeptins sensitize multidrug-resistant Gram-negative pathogens to antibiotics

Award Number: R21AI146693

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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