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Phages as drivers of pathogenicity: selective impacts and molecular targets of clinical Pseudomonas aeruginosa phages

Award Number: R21AI143296
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 Chronic infections are a major and rising medical challenge, often characterized by varying pathogen virulence and drug resistance profiles. Pseudomonas aeruginosa (PA) is a key driver of chronic infection mortality, including in our focal system of lung infections in Cystic Fibrosis (CF) patients. While PA has been studied extensively, the role of naturally occurring bacteriophages (phages) in shaping the evolutionary dynamics of chronic infections has been largely overlooked. It is recognized that within the CF lung there are high levels of phage, and in vitro work suggests that phage are potential drivers of bacterial diversity and of shifts in virulence. Phages bind to specific bacterial surface factors to initiate infection, including receptors that are important for virulence and antibiotic resistance, such as LPS, type IV pili, or efflux pumps. Thus phages can in principle impart selection on a pathogenic bacterium that impacts virulence and antibiotic resistance changing the trajectory of chronic infections. While naturally present phages have been largely overlooked in an infection context, phage therapy continues to draw attention and mixed results. In order to understand the drivers of pathogen evolution in an infection context, and to assess the potential for phage therapy as a curative and/or selective agent, it is essential to map the selective impacts and molecular targets of phages within infection settings. The overarching hypothesis of this study is that introduced and endemic phages shape the evolution of pathogen surface factors, which in turn define pathogen virulence and drug / phage resistance. This project will test this hypothesis using an array of genomic, phenotypic and modeling techniques with the goal of opening paths towards improved mechanisms of control.


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: 2022 ( Subtotal = -$2,432 )
2022	2020	GEORGIA TECH RESEARCH CORPORATION	926 DALNEY ST NW	ATLANTA	GA	30332	FULTON	USA	Allergy and Infectious Diseases Research	000	2	5/2/2022	NON-COMPETING CONTINUATION	-$2,432
														Subtotal = -$2,432

Issue Date FY: 2020 ( Subtotal = $197,250 )
2020	2020	GEORGIA TECH RESEARCH CORPORATION	926 DALNEY ST NW	ATLANTA	GA	30318	FULTON	USA	Allergy and Infectious Diseases Research	000	2	11/5/2019	NON-COMPETING CONTINUATION	$197,250
														Subtotal = $197,250

Issue Date FY: 2019 ( Subtotal = $236,700 )
2019	2019	GEORGIA TECH RESEARCH CORPORATION	505 10TH ST NW	ATLANTA	GA	30318	FULTON	USA	Allergy and Infectious Diseases Research	000	1	11/19/2018	NEW	$236,700
														Subtotal = $236,700

Grand Total All Awards = $431,518

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Phages as drivers of pathogenicity: selective impacts and molecular targets of clinical Pseudomonas aeruginosa phages

Award Number: R21AI143296

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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