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Functional contribution of metallophore biosynthetic gene clusters to plasmid conjugation and bacterial virulence and pathogenicity.

Award Number: F32AI202844
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 09/01/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2029

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Functional contribution of metallophore biosynthetic gene clusters to plasmid conjugation and bacterial virulence and pathogenicity. - PROJECT SUMMARY/ABSTRACT The global emergence of multidrug resistant (MDR) bacteria is primarily fueled by the direct, horizontal transfer of whole antimicrobial resistance (AMR) genes directly between bacteria. This direct transfer is mediated by conjugative plasmids, extrachromosomal, self replicating and transferable DNA elements that enable the whole transfer of AMR genes along with virulence and metabolic genes. Co-transfer of AMR genes as well as virulence and metabolic genes is highly prevalent in the gut of humans and other animals, but is understudied. This co-transfer is critically important as it results not only in pathogens with increased resistance to therapeutic treatment, but results results not only in pathogens with increased resistance, but drives the evolution of strains that demonstrate enhanced persistence and virulence, significantly contributing to increased clinical morbidity and mortality. This project challenges the current AMR paradigm by hypothesizing that conjugative plasmids are powerfully selected based on co-transferred fitness-enhancing virulence traits, specifically metal scavenging (metallophores), rather than solely by antibiotic pressure. We focus centrally on metallophore biosynthetic gene clusters (BGCs), which are critical for survival and pathogenicity in metal-limited host environments. This research will employ three integrated aims: (Aim 1) Define the clinical prevalence and co-localization of metallophore BGCs and plasmid features via bioinformatic correlation; (Aim 2) Determine the functional metallophore transfer and expression dynamics via metabolomics; and (Aim 3) Quantify the contribution of plasmid-encoded metallophores to pathogenicity using rigorous in vitro and in vivo fitness assays. The successful validation of this hypothesis will demonstrate that plasmid-encoded metallophores are key drivers of bacterial fitness and virulence, providing new, non-antibiotic-based avenues for targeting plasmid maintenance and metal scavenging pathways to combat MDR pathogens.


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: 2026 ( Subtotal = $79,780 )
2026	2026	UNIVERSITY OF DENVER	2199 S UNIVERSITY BLVD RM 222	DENVER	CO	80210	DENVER	USA	Allergy and Infectious Diseases Research	000	1	7/24/2026	NEW	$79,780
2026	2026	UNIVERSITY OF DENVER	2199 S UNIVERSITY BLVD RM 222	DENVER	CO	80210	DENVER	USA	Allergy and Infectious Diseases Research	001	1	8/28/2026	NEW	$0
														Subtotal = $79,780

Grand Total All Awards = $79,780

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Functional contribution of metallophore biosynthetic gene clusters to plasmid conjugation and bacterial virulence and pathogenicity.

Award Number: F32AI202844

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 09/01/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2029

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