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Investigating the mechanism of infection and therapeutic potential of Pseudomonas nucleus-forming phages

Award Number: F30AI176696
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

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Project Summary Nucleus-forming bacteriophages (phages) are a recently discovered class of lytic phages that protect their genome by encapsulating it in a nucleus-like protein shell (phage nucleus). The goal of the proposed research is to determine whether the unique properties of nucleus-forming phages make them advantageous therapies for human Pseudomonas aeruginosa infections. ΦKZ and ΦPA3 are nucleus-forming phages that infect P. aeruginosa and demonstrate the ability to selectively localize proteins to their phage nucleus and exclude others, including DNA-targeting bacterial phage defense proteins. Preliminary data show that ΦKZ gp69 is a conserved protein in P. aeruginosa nucleus-forming phages and plays a key role in mediating selective protein trafficking into the phage nucleus. This research will determine the structure of gp69 in complex with other nuclear shell-associated proteins, the mechanism by which gp69 mediates protein transport into the phage nucleus, and other factors that facilitate transport into the phage nucleus. Furthermore, this research will determine the motifs that signal a protein to be imported into the phage nucleus, how those motifs differ between P. aeruginosa infecting phage, and the competitive advantages selective protein import imparts on nucleus-forming phages. Lastly, resistance to phages is known to select for costly evolutionary trade-offs in the host bacterium. This research will determine how pathogenicity and antibiotic sensitivity are altered in P. aeruginosa resistant to nucleus-forming phages. Together, the results of this study will provide crucial information for the development of nucleus-forming phage therapeutics.


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: 2025 ( Subtotal = $42,100 )
2025	2025	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	2	11/21/2024	NON-COMPETING CONTINUATION	$42,100
														Subtotal = $42,100

Issue Date FY: 2024 ( Subtotal = $41,666 )
2024	2024	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Allergy and Infectious Diseases Research	001	1	12/27/2023	NEW	$0
2024	2024	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Allergy and Infectious Diseases Research	002	1	1/5/2024	NEW	$0
2024	2024	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Allergy and Infectious Diseases Research	003	1	5/8/2024	NEW	$1,280
2024	2024	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DRIVE	LA JOLLA	CA	92093	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	1	12/6/2023	NEW	$40,386
														Subtotal = $41,666

Grand Total All Awards = $83,766

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Investigating the mechanism of infection and therapeutic potential of Pseudomonas nucleus-forming phages

Award Number: F30AI176696

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

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