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Impact of Commensal Corynebacterium Species on Pathogen Colonization and Microbiota Composition

Award Number: R01GM117174
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/01/2016
PERIOD OF PERFORMANCE END DATE: 01/31/2021

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Impact of Commensal Corynebacterium Species on Pathogen Colonization and Microbiota Composition - DESCRIPTION (provided by applicant): Functional studies to elucidate mechanistic interactions between different bacterial species within the human microbiome are critically needed to understand their role in this microbial community. Research suggests that non-diphtheriae Corynebacterium species play a significant role in structuring healthy nasal and skin microbiota. These generally harmless commensals are implicated in affecting colonization by Staphylococcus aureus and Streptococcus pneumoniae, pathogens that also frequently colonize nasal/skin sites. Our data indicate that some Corynebacterium species hydrolyze analogs of human skin-surface lipids releasing free fatty acids (FFAs) with anti-pneumococcal activity. Thus, we hypothesize that Corynebacterium spp. modify their habitat by producing lipases that release FFAs with antibacterial activity from host epithelial-surface lipids and that the level of these lipid substrates impacts the composition of the skin microbiota, diminishing pathogen colonization. The overall objective of this proposal is to gain genetic and mechanistic knowledge of how commensal Corynebacterium spp. release these antibacterial FFAs from host surface lipids and to determine if altering skin lipid composition affects microbiota composition. The rationale for this study is that uncovering these mechanisms will create opportunities to identify specific strains, genes and/or Corynebacterium-produced compounds with potential for therapeutic use. We will use a combination of culture-based approaches and human samples to identify relevant genes, and the impact of their expression, in culture and on epithelial surfaces. The Specific Aims of this proposal are (1) to determine how Corynebacterium spp. release antibacterial free fatty acids from host lipids, (2) to identify and characterize the regulatory mechanisms that control activity of extracellular lipases in lipid-requiring and lipid-independent Corynebacterium spp. and (3) to determine the impact of a topically applied skin-surface-lipid analog on the microbiota of three different human skin sites (dry, moist and oily). To accomplish these, we will use a combination of genetic, biochemical and bioinformatic approaches (Aims 1 and 2), along with a 16S rRNA gene-based approach (Aim 3). The significance of this work will be to provide the foundational mechanistic information that is critically needed to identify specifc strains of Corynebacterium spp. and Corynebacterium-produced compounds with potential as alternative, non-antibiotic therapies to prevent infections by pathogens, such as S. pneumoniae and S. aureus. The three main innovations in our strategy are (1) using functional molecular studies of bacteria in coculture to elucidate the role of different bacterial species within the human microbiome, (2) choosing a system that allows for non-invasive studies directly in the human host, and (3) translating our findings to test a simple intervention on human skin surfaces. Our long-term goal is to develop new and sustainable ways to manage the composition of nasal and skin microbiota to prevent disease by excluding or controlling pathogens.


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: 2021 ( Subtotal = -$6,660 )
2021	2019	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Biomedical Research and Research Training	000	5	8/10/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$6,660
														Subtotal = -$6,660

Issue Date FY: 2020 ( Subtotal = -$71,373 )
2020	2019	FORSYTH DENTAL INFIRMARY FOR CHILDREN	245 FIRST ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Biomedical Research and Research Training	002	4	9/5/2020	NON-COMPETING CONTINUATION	-$6,660
2020	2019	FORSYTH DENTAL INFIRMARY FOR CHILDREN	245 FIRST ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Biomedical Research and Research Training	000	4	3/31/2020	NON-COMPETING CONTINUATION	-$375,347
2020	2019	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Biomedical Research and Research Training	003	5	9/5/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$6,660
2020	2019	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Biomedical Research and Research Training	001	5	4/1/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$303,974
														Subtotal = -$71,373

Issue Date FY: 2019 ( Subtotal = $395,905 )
2019	2019	FORSYTH DENTAL INFIRMARY FOR CHILDREN	245 FIRST ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Biomedical Research and Research Training	000	4	1/23/2019	NON-COMPETING CONTINUATION	$395,905
														Subtotal = $395,905

Issue Date FY: 2018 ( Subtotal = $416,892 )
2018	2018	FORSYTH DENTAL INFIRMARY FOR CHILDREN	245 FIRST ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Biomedical Research and Research Training	000	3	1/22/2018	NON-COMPETING CONTINUATION	$369,565
2018	2018	FORSYTH DENTAL INFIRMARY FOR CHILDREN	245 FIRST ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Biomedical Research and Research Training	001	3	5/24/2018	NON-COMPETING CONTINUATION	$47,327
														Subtotal = $416,892

Issue Date FY: 2017 ( Subtotal = $411,972 )
2017	2017	FORSYTH DENTAL INFIRMARY FOR CHILDREN	245 FIRST ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Biomedical Research and Research Training	002	2	7/19/2017	SUPPLEMENT FOR EXPANSION	$13,455
2017	2017	FORSYTH DENTAL INFIRMARY FOR CHILDREN	245 FIRST ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Biomedical Research and Research Training	001	2	1/23/2017	NON-COMPETING CONTINUATION	$358,664
2017	2017	FORSYTH DENTAL INFIRMARY FOR CHILDREN	245 FIRST ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Biomedical Research and Research Training	003	2	8/2/2017	NON-COMPETING CONTINUATION	$39,853
2017	2016	FORSYTH DENTAL INFIRMARY FOR CHILDREN	245 FIRST ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Biomedical Research and Research Training	000	1	1/19/2017	NEW	$0
														Subtotal = $411,972

Issue Date FY: 2016 ( Subtotal = $376,965 )
2016	2016	Forsyth Dental Infirmary for Children Forsyth Institute	140 FENWAY	BOSTON	MA	02115	SUFFOLK	USA	Biomedical Research and Research Training	000	1	1/22/2016	NEW	$376,965
														Subtotal = $376,965

Grand Total All Awards = $1,523,701

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Impact of Commensal Corynebacterium Species on Pathogen Colonization and Microbiota Composition

Award Number: R01GM117174

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/01/2016

PERIOD OF PERFORMANCE END DATE: 01/31/2021

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