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Bacteriophages as Modulators of Bacterial Colonization

Award Number: K01AI166096
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 12/13/2021
PERIOD OF PERFORMANCE END DATE: 07/31/2025

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Bacteriophages as Modulators of Bacterial Colonization - PROJECT SUMMARY Multidrug-resistant organisms (MDROs) remain major causes of morbidity and mortality in hematopoietic cell transplant (HCT) recipients. Because of the substantial use of antibiotics in these patients, their gut microbiome balance is perturbed and becomes dominated by MDROs, vancomycin-resistant enterococci (VRE) in particular. This disturbance is associated with subsequent invasive infections such as bacteremia that can lead to fatal outcome. Restoration of the normal balance of the gut flora and reduction or control of MDRO colonization may curtail these complications and improve outcomes. One innovative approach to restore the microbiome balance of the gut flora and reduce colonization with MDROs in HCT recipients is the administration of bacteriophages (i.e., phages). Phages are ubiquitous and natural entities, present in the environment and in our bodies, and capable of lysing specific pathogens without disturbing the host’s normal flora while averting the collateral damage of antimicrobial usage. My long-term research goal is to understand how phages contribute to host-microbe interactions and their overall impact on the health of HCT recipients. Our preliminary data indicate that VRE colonization can cause inflammation in the gut of germ-free wild-type mice. Additionally, we found that phages are present in high numbers in HCT patients’ stool samples and that VRE phages can be recovered from environmental samples and can lyse a variety of VRE strains in a larva model. The objective of the proposed research is to investigate the interactions between phages, the gut bacterial microbiome, and host responses in VRE-colonized HCT recipients and to identify biomarkers in the gut phage population predisposing patients to complications such as bacterial infections or graft versus host disease. The central hypothesis for this project is that VRE phages can restore balance in the gut microbiota by reducing inflammation and VRE colonization in HCT recipients. My ultimate goal is to generate significant findings and new hypotheses for an R01 application aiming at (1) optimizing the design of a chemotherapy- treated bone marrow-reconstituted mouse model mimicking the condition of HCT patients, (2) testing the efficacy of phages and phages+antibiotic synergy in preventing major MDRO infections in this mouse model, and (3) validating the role of certain phage populations in predicting and preventing poor outcomes. The rationale is that this line of work will provide supportive evidence for future development and evaluation of a phage-based intervention in humans. My long-term career goal is to become a leading investigator with expertise in the design of effective and safe phage-based natural therapeutic products that may restore a healthy gut microbiota and curtail serious complications encountered in HCT recipients (i.e., MDROs), thus improving their overall health outcomes. The proposal will aid in the fight against MDROs by curtailing the incidence of MDRO colonization and infections and by improving survival and quality-of-life of HCT recipients.


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 = $105,792 )
2026	2026	THE UNIVERISTY OF TEXAS M.D. ANDERSON CANCER CENTER	1515 HOLCOMBE BLVD	HOUSTON	TX	77030	HARRIS	USA	Allergy and Infectious Diseases Research	001	5	12/23/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$105,792
2026	2025	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Allergy and Infectious Diseases Research	002	4	2/10/2026	NON-COMPETING CONTINUATION	$0
2026	2025	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Allergy and Infectious Diseases Research	000	4	12/23/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $105,792

Issue Date FY: 2025 ( Subtotal = $105,792 )
2025	2025	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Allergy and Infectious Diseases Research	000	4	11/25/2024	NON-COMPETING CONTINUATION	$105,792
														Subtotal = $105,792

Issue Date FY: 2024 ( Subtotal = $105,792 )
2024	2024	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Allergy and Infectious Diseases Research	000	3	11/1/2023	NON-COMPETING CONTINUATION	$105,792
														Subtotal = $105,792

Issue Date FY: 2023 ( Subtotal = $105,792 )
2023	2023	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Allergy and Infectious Diseases Research	000	2	11/30/2022	NON-COMPETING CONTINUATION	$105,792
														Subtotal = $105,792

Issue Date FY: 2022 ( Subtotal = $105,792 )
2022	2022	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Allergy and Infectious Diseases Research	000	1	12/13/2021	NEW	$105,792
														Subtotal = $105,792

Grand Total All Awards = $528,960

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Bacteriophages as Modulators of Bacterial Colonization

Award Number: K01AI166096

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 12/13/2021

PERIOD OF PERFORMANCE END DATE: 07/31/2025

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