Wednesday, May 1, 2024 5/1/2024

Transcriptomic and Genetic Differences of Group A Streptococcus in Humans: Acute Infection versus Carriage

Award Number: R21AI147502
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/ABSTRACT Acute pharyngitis is the most common illness for which children and adults seek acute medical care. Group A streptococcus (GAS) is the most frequent bacterial cause of pharyngitis in children and causes both suppurative (acute otitis media, acute sinusitis, mastoiditis) and non-suppurative (post-streptococcal glomerulonephritis and acute rheumatic fever) sequelae. Furthermore, GAS has emerged as a major cause of severe invasive disease including streptococcal toxic shock syndrome and necrotizing fasciitis. The carrier state of GAS is of particular significance to public health as carriers serve as a reservoir for spread of the pathogen to others in the population. GAS carriage has been associated with community outbreaks of pharyngitis, nosocomial infections and fatal invasive disease in individuals who are close contacts of carriers. To date, no study has demonstrated the physiological characteristics of GAS as it exists in the carrier state in human patients. The main goal of this proposal is to define the transcriptomic and genomic differences of GAS between two states of human colonization: acute infection (in children with pharyngitis) and the carrier state (in asymptomatic children with positive pharyngeal cultures after treatment). Due to the challenge in obtaining longitudinal samples from human subjects, to date there are no reports of such analyses. Not only will these results be the first of their kind, but we anticipate they will be the most direct and comparable analyses from human subjects colonized with GAS during different stages of infection and colonization. We hypothesize that, when in the carrier state, GAS exhibits unique transcriptional profiles that differ from those of the acute infection state. We expect transcriptional profiles of GAS to provide important information regarding the changes the organism undergoes when transitioning between acute infection and carriage. Previous studies have posited that genetic differences between organisms in these two states may also account for differences in carriage potential. We will test these two hypotheses using longitudinal human samples. Children with acute GAS pharyngitis will be recruited and enrolled in the study. Following treatment, children who become GAS carriers will be identified. The specific goals of this proposal are to 1) demonstrate the transcriptomic profiles and genetic differences in GAS recovered from individuals with acute pharyngitis compared to GAS recovered from carriers and 2) employ in vitro and tissue culture models of carriage to determine how differentially expressed genes or genetic mutations affect colonization potential of GAS. Overall, this proposal will offer the first data on the transcriptomics of GAS carrier state in a human host and will provide invaluable information on both the genetic and transcriptional changes GAS undergoes when switching from a pathogenic to colonization state in the only natural host. Furthermore, these results may be generalized to other pathobiont bacterial species that shift their relationship to the host from pathogen to commensal.


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: 2024 ( Subtotal = -$17,106 )
2024	2020	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	4400 VESTAL PKWY E	BINGHAMTON	NY	13902	BROOME	USA	Allergy and Infectious Diseases Research	000	2	3/26/2024	NON-COMPETING CONTINUATION	-$17,106
														Subtotal = -$17,106

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2020	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	4400 VESTAL PKWY E	BINGHAMTON	NY	13902	BROOME	USA	Allergy and Infectious Diseases Research	000	2	7/19/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $208,598 )
2020	2020	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	4400 VESTAL PKWY E	BINGHAMTON	NY	13902	BROOME	USA	Allergy and Infectious Diseases Research	000	2	6/17/2020	NON-COMPETING CONTINUATION	$208,598
														Subtotal = $208,598

Issue Date FY: 2019 ( Subtotal = $247,805 )
2019	2019	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	4400 VESTAL PKWY E	BINGHAMTON	NY	13902	BROOME	USA	Allergy and Infectious Diseases Research	000	1	7/10/2019	NEW	$247,805
														Subtotal = $247,805

Grand Total All Awards = $439,297

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Transcriptomic and Genetic Differences of Group A Streptococcus in Humans: Acute Infection versus Carriage

Award Number: R21AI147502

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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