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Investigating the Role of S. aureus Citrate Metabolism in Prosthetic Joint Infection

Award Number: F31AI197749
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 04/01/2026
PERIOD OF PERFORMANCE END DATE: 03/31/2028

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Investigating the Role of S. aureus Citrate Metabolism in Prosthetic Joint Infection - Prosthetic joint infection (PJI) is a complication following arthroplasty that occurs in approximately 1-3% of patients, with ~50% of cases caused by methicillin-resistant Staphylococcus aureus (S. aureus). Biofilm formation evolves as bacteria multiply, producing a complex extracellular matrix that creates a heterogeneous population with unique metabolic properties. S. aureus is metabolically flexible, allowing it to colonize various niches and establish chronic infections. Bacterial-derived metabolites play an important role in biofilm infection, which is reflected by the fact that several tricarboxylic acid cycle (TCA) intermediates are critical for biofilm development. Our laboratory has characterized an in vivo mouse model of PJI and identified macrophages (Mφs), anti-inflammatory granulocytic myeloid-derived suppressor cells (G-MDSCs), and polymorphonuclear cells (PMNs) as the predominant leukocyte infiltrates, all of which are also present in human PJI. Previous work from our group has characterized several metabolites that are important for promoting S. aureus persistence during PJI; however, it is unclear how S. aureus adapts in response to leukocyte exposure to regulate its metabolism to promote biofilm formation and establishment. Our novel bacterial single-cell RNA sequencing (Bsc-RNA seq) approach has revealed that Mφs, G-MDSCs, and PMNs elicit distinct metabolic changes in S. aureus biofilm, namely, the expression of genes involved in citrate metabolism (gltA, acnA, and icd). While the role of AcnA has been examined in a S. aureus skin and soft tissue infection model, its role, along with the other citrate enzymes (GltA and Icd) in biofilm development under leukocyte pressure and during PJI, remains elusive. The overarching hypothesis of this fellowship is that S. aureus citrate metabolism is upregulated to adapt to leukocyte pressure and promote biofilm development and pathogenesis. The role of citrate metabolism in biofilm development and S. aureus pathogenicity will be examined in the following Specific Aims. 1) Investigate the role of S. aureus biofilm citrate metabolism under leukocyte pressure and 2) Elucidate the role of citrate metabolism on S. aureus pathogenesis in PJI. The results from this fellowship will provide new insights into S. aureus metabolic adaptations under leukocyte pressure and within the PJI niche that could represent future therapeutic targets.


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 = $41,509 )
2026	2026	BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA	4215 EMILE ST	OMAHA	NE	68105	DOUGLAS	USA	Allergy and Infectious Diseases Research	003	1	4/1/2026	NEW	$0
2026	2026	BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA	4215 EMILE ST	OMAHA	NE	68105	DOUGLAS	USA	Allergy and Infectious Diseases Research	001	1	4/1/2026	NEW	$576
2026	2026	BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA	4215 EMILE ST	OMAHA	NE	68105	DOUGLAS	USA	Allergy and Infectious Diseases Research	000	1	3/27/2026	NEW	$40,933
2026	2026	BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA	4215 EMILE ST	OMAHA	NE	68105	DOUGLAS	USA	Allergy and Infectious Diseases Research	002	1	4/1/2026	NEW	$0
														Subtotal = $41,509

Grand Total All Awards = $41,509

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Investigating the Role of S. aureus Citrate Metabolism in Prosthetic Joint Infection

Award Number: F31AI197749

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 04/01/2026

PERIOD OF PERFORMANCE END DATE: 03/31/2028

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