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Identifying Risk Factors for Antibiotic Resistance via Integration of Epidemiology and Metagenomics

Award Number: K01AI143881
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 01/18/2019
PERIOD OF PERFORMANCE END DATE: 04/30/2024

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Identifying Risk Factors for Antibiotic Resistance via Integration of Epidemiology and Metagenomics - PROJECT SUMMARY Given the growing burden of antimicrobial resistance (AR) and lack of effective therapies for multi-drug resistant organisms, the development of new tools or models which risk-stratify patients for colonization and infection by AR bacteria is of paramount importance, particularly in high-risk populations. The significance of the gut microbiome in mediating colonization resistance against drug resistant pathogens as well as the role of microbiota-depleting antibiotics in the development of AR infections is being increasingly appreciated. However, there is currently a deficiency of methods integrating microbiome and antibiotic factors into AR- predictive algorithms. Thus, the overall objective of the proposed research is to improve understanding of the factors driving the epidemiology of AR-colonization and infection by incorporating metagenomic and antibiotic administration data of a well-defined clinical cohort. In this proposal, we focus on patients with acute myelogenous leukemia (from whom we have already collected extensive longitudinal stool samples and performed 16S rRNA gene sequencing) because of the high rates of AR pathogen colonization and severe risk for infection. The overarching hypothesis that will be tested is that the baseline presence of a limited number of key bacterial species and antibiotic resistance genes (ARGs) are critical for the risk of colonization and/or infection with an AR pathogen when combined with the administration of specific antimicrobials. We will begin our research by comprehensively determining the epidemiology of AR pathogen colonization and AR infection in our cohort via culture based stool sample analyses and clinical chart review, respectively. Using shotgun metagenomics, we will establish whether the baseline intestinal microbiome species and resistome characteristics are associated with the acquisition of AR pathogens colonizing or causing infection. Similarly, we will ascertain the relationship between antimicrobial exposure, microbiome disruption, and subsequent AR emergence. The data from these studies will be integrated into Decision Tree (DT) and Random Forest (RF) models to improve the prediction of AR pathogen colonization and AR infection outcomes. The proposed career development award, which utilizes the expertise of a superlative mentorship team and a uniquely designed research and training plan, will enable me the opportunity to build upon my current expertise in microbiology, genomics, and molecular epidemiology by adding advanced training in shotgun metagenomic analyses, bioinformatics, and biostatistical modeling. Moreover, the numerous resources and support provided by my institution and mentoring team will ensure my successful transition to an independent investigator as well as establish a strong foundation for my long-term goals of understanding and mitigating the impact of antimicrobial resistance in human health via integration of multiple –omics platforms and provision of personalized genomic-based medicine.


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 = -$386 )
2025	2023	TEXAS A&M AGRILIFE RESEARCH	2147 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Allergy and Infectious Diseases Research	000	5	12/19/2024	NON-COMPETING CONTINUATION	-$386
														Subtotal = -$386

Issue Date FY: 2023 ( Subtotal = $108,000 )
2023	2023	TEXAS A&M AGRILIFE RESEARCH	2147 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Allergy and Infectious Diseases Research	000	5	12/9/2022	NON-COMPETING CONTINUATION	$108,000
														Subtotal = $108,000

Issue Date FY: 2022 ( Subtotal = $108,000 )
2022	2022	TEXAS A&M AGRILIFE RESEARCH	2147 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Allergy and Infectious Diseases Research	000	4	1/19/2022	NON-COMPETING CONTINUATION	$108,000
														Subtotal = $108,000

Issue Date FY: 2021 ( Subtotal = $108,000 )
2021	2021	TEXAS A&M AGRILIFE RESEARCH	2147 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Allergy and Infectious Diseases Research	001	3	3/11/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$108,000
2021	2021	TEXAS A&M AGRILIFE RESEARCH	2147 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Allergy and Infectious Diseases Research	003	3	9/2/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$37,434
2021	2020	UNIVERSITY OF TEXAS M. D. ANDERSON CANCER CENTER, THE	1515 HOLCOMBE BLVD	HOUSTON	TX	77030	HARRIS	USA	Allergy and Infectious Diseases Research	002	2	9/2/2021	NON-COMPETING CONTINUATION	-$37,434
2021	2020	UNIVERSITY OF TEXAS M D ANDERSON CANCER CENTER	1515 HOLCOMBE BLVD UNIT 207	HOUSTON	TX	77030	HARRIS	USA	Allergy and Infectious Diseases Research	000	2	3/11/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $108,000

Issue Date FY: 2020 ( Subtotal = $110,387 )
2020	2020	UNIVERSITY OF TEXAS M D ANDERSON CANCER CENTER	1515 HOLCOMBE BLVD UNIT 207	HOUSTON	TX	77030	HARRIS	USA	Allergy and Infectious Diseases Research	000	2	1/7/2020	NON-COMPETING CONTINUATION	$110,387
														Subtotal = $110,387

Issue Date FY: 2019 ( Subtotal = $110,387 )
2019	2019	UNIVERSITY OF TEXAS M D ANDERSON CANCER CENTER	1515 HOLCOMBE BLVD UNIT 207	HOUSTON	TX	77030	HARRIS	USA	Allergy and Infectious Diseases Research	000	1	1/18/2019	NEW	$110,387
														Subtotal = $110,387

Grand Total All Awards = $544,388

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Identifying Risk Factors for Antibiotic Resistance via Integration of Epidemiology and Metagenomics

Award Number: K01AI143881

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 01/18/2019

PERIOD OF PERFORMANCE END DATE: 04/30/2024

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