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Myxobacterial predatory antimicrobial production in response to quorum sensing signal interception

Award Number: R15AI137996
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 30-year absence of a clinically approved natural product-derived antibiotic with a novel scaffold demonstrates the dire need for unique methods to access new antimicrobial scaffolds and activities. However, the recent surge in scrutiny of microbial genomes provides evidence to indicate that an abundance of chemical scaffolds hidden within nascent biosynthetic pathways (BSPs) remain undiscovered. Predatory myxobacteria have contributed over 600 distinct natural products to the microbial chemical space including 42 novel scaffolds of which 29 exhibit antibacterial or antifungal activities in the last 6 years alone. Myxobacteria exemplify the abundance of untapped chemical space with large bacterial genomes replete with BSPs that typically account for 10% of their total genomic content. However, unlike natural product isolations from other organisms such as plants or marine sponges sequestered directly from competitive surroundings, bacterial extracts from the ecologically robust soil microbiome often omit chemical entities below current detection levels. Instead, bacterial natural products are predominately isolated from axenic cultivation of a producing species removed from community maintenance and competition. We hypothesize that myxobacterial cultivation conditions that induce predation either through supplementation with exogenous quorum sensing molecules (QSMs) or non-axenic, co-cultivation with QSM-producing quarry will result in production of antimicrobial new chemical entities (NCEs). We intend to establish graduate and undergraduate student-led molecular networking of mass spectrometry datasets collected from the cultivation of 13 myxobacteria using these conditions facilitated by the Global Natural Products Social Molecular Networking (GNPS) open access platform to efficiently identify resulting NCEs for further antimicrobial assessment. These molecular networking efforts will publically available molecular networks that will represent the chemical space available to QSM- exposed myxobacteria and significantly benefit dereplication and discovery efforts. Our conservative expectation of 1-2 NCEs per investigated myxobacterial predator would provide a total of 13-26 potential antimicrobial NCEs upon completion of the proposed research.


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 = -$9,562 )
2024	2019	THE UNIVERSITY OF MISSISSIPPI	113 FALKNER	UNIVERSITY	MS	38677	LAFAYETTE	USA	Allergy and Infectious Diseases Research	000	1	11/16/2023	NEW	-$9,562
														Subtotal = -$9,562

Issue Date FY: 2019 ( Subtotal = $422,422 )
2019	2019	UNIVERSITY OF MISSISSIPPI	113 FALKNER	UNIVERSITY	MS	38677	LAFAYETTE	USA	Allergy and Infectious Diseases Research	000	1	8/22/2019	NEW	$422,422
														Subtotal = $422,422

Grand Total All Awards = $412,860

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Myxobacterial predatory antimicrobial production in response to quorum sensing signal interception

Award Number: R15AI137996

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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