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Antimicrobial susceptibility associations in Acinetobacter baumannii based on genomic and transcriptomic analyses

Award Number: R21AI121738
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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¿ DESCRIPTION (provided by applicant): Acinetobacter baumannii is a dangerous nosocomial pathogen associated with antimicrobial resistance in clinical infections. Although traditional antimicrobial resistance characterization relies on susceptibility testing in research or clinical laboratories, databases of resistance-associated genes are now available to characterize resistance profiles, based on the analysis of whole-genome sequence (WGS) data. In this study, we propose to sequence 100 isolates that currently have associated antimicrobial resistance data in order to better understand mechanisms associated with antimicrobial resistance. WGS data from paired resistant/susceptible isolates, based on a shared phylogenetic history, will be compared to identify both single nucleotide polymorphisms (SNPs) and coding regions associated with the resistance phenotype. A genome-wide association study (GWAS) will be employed in this study to identify SNPs and genes associated with the antimicrobial resistance phenotype. In addition to sequencing these isolates, we also propose to comprehensively characterize the antimicrobial resistance profile to associate specific antimicrobials with specific genetic features. These results are expected to generate more accurate and descriptive genotype/phenotype associations than currently exist. In addition to genomics approaches, transcriptomic methods are proposed to better understand the contribution of gene expression to the antimicrobial resistance phenotype. We will sequence extracted RNA from paired resistant/susceptible isolates grown in media with and without sub-inhibitory concentrations of antimicrobials. Differential gene expression will be identified between paired isolates to find correlations between antimicrobial resistance and gene expression. Additional antimicrobials will be tested with quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) to identify if observed transcriptional differences are associated with multiple classes of antimicrobials. In general, this proposed work is anticipated to identify novel mechanisms associated with antimicrobial resistance as well as increase the target specificity of previously associated mechanisms. These goals will not only help in the design of more informative diagnostics, but will also aid in accurate detection of antimicrobial resistance, which will also help in the more timely and focused treatment of resistant clinical infections.


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: 2020 ( Subtotal = -$14,143 )
2020	2017	NORTHERN ARIZONA UNIVERSITY	601 S KNOLES DR ROOM 220	FLAGSTAFF	AZ	86011	COCONINO	USA	Allergy and Infectious Diseases Research	000	2	12/10/2019	NON-COMPETING CONTINUATION	-$14,143
														Subtotal = -$14,143

Issue Date FY: 2019 ( Subtotal = $0 )
2019	2017	NORTHERN ARIZONA UNIVERSITY	601 S KNOLES DR ROOM 220	FLAGSTAFF	AZ	86011	COCONINO	USA	Allergy and Infectious Diseases Research	000	2	1/23/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2017 ( Subtotal = $259,815 )
2017	2017	NORTHERN ARIZONA UNIVERSITY	601 S KNOLES DR ROOM 220	FLAGSTAFF	AZ	86011	COCONINO	USA	Allergy and Infectious Diseases Research	000	2	12/22/2016	NON-COMPETING CONTINUATION	$259,815
														Subtotal = $259,815

Issue Date FY: 2016 ( Subtotal = $230,875 )
2016	2016	NORTHERN ARIZONA UNIVERSITY	PO BOX 4096	FLAGSTAFF	AZ	86011	COCONINO	USA	Allergy and Infectious Diseases Research	000	1	12/21/2015	NEW	$230,875
2016	2016	NORTHERN ARIZONA UNIVERSITY	PO BOX 4096	FLAGSTAFF	AZ	86011	COCONINO	USA	Allergy and Infectious Diseases Research	001	1	6/28/2016	NEW	$0
														Subtotal = $230,875

Grand Total All Awards = $476,547

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Antimicrobial susceptibility associations in Acinetobacter baumannii based on genomic and transcriptomic analyses

Award Number: R21AI121738

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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