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Characterizing the function and regulation of a conserved virulence-associated genetic pathway of pathogenic Alphaproteobacteria

Award Number: R15GM135933
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: 10/11/2022
PERIOD OF PERFORMANCE END DATE: 08/31/2023

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Characterizing the function and regulation of a conserved virulence-associated genetic pathway of pathogenic Alphaproteobacteria - PROJECT SUMMARY Pathogenic bacteria employ myriad processes to cause human disease, and these processes include biofilm formation, chemotaxis and motility, and the implementation of secretion systems, all of which ultimately aid in establishing intimate associations between the bacterium and the host. Several medically important bacteria, including some human pathogenic Alphaproteobateria, are extremely difficult to grow, handle, and/or manipulate, and thus, many of the basic virulence mechanisms related to the processes mentioned above are poorly defined in these organisms. Therefore, there are many benefits, including novel therapeutic and vaccine development that may be gleaned from defining broadly conserved bacterial virulence mechanisms. Considering members of the Alphaproteobacteria, the plant pathogen Agrobacterium tumefaciens serves as an exemplary model for studying basic virulence mechanisms that are highly conserved among the Alphaproteobacteria, including those causing human disease. A. tumefaciens is a free-living soil bacterium that senses and responds to signals released from wounded plants, resulting in bacterial chemotaxis toward the wounded plant. A. tumefaciens subsequently employs a type IV secretion system to transfer a T-DNA complex into the cells of the plant. This conjugation event leads to the formation of crown gall tumors, which are severely detrimental to the plant. Preliminary results indicate a LysR-type transcriptional regulator, VtlR (for virulence-associated transcriptional LysR-family regulator) is required for efficient A. tumefaciens-mediated tumor formation. Preliminary data demonstrate that an A. tumefaciens vtlR deletion strain produces fewer and less robust tumors in potatoes compared to the parental strain, and moreover, the vtlR deletion strain exhibits significant defects in biofilm formation. Transcriptomic analyses revealed that VtlR controls the expression of a small regulatory RNA (sRNA) called AbcR1, as well as a multitude of other genes related to conjugation systems, nutrient uptake, and virulence. The VtlR orthologue in the closely related alphaproteobacterium Brucella abortus is required for virulence in an animal model of infection, and thus, VtlR-family regulators are highly conserved and appear to be required for host-bacteria interactions in the Alphaproteobacteria. Therefore, the systematic characterization of VtlR in A. tumefaciens will significantly illuminate the mechanism by which this transcriptional regulator is linked to virulence in Alphaproteobacteria.


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 = -$61,305 )
2024	2019	ROWAN UNIVERSITY	201 MULLICA HILL RD	GLASSBORO	NJ	08028	GLOUCESTER	USA	Biomedical Research and Research Training	000	3	1/5/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$61,305
														Subtotal = -$61,305

Issue Date FY: 2023 ( Subtotal = -$163 )
2023	2019	SAINT JOSEPHS UNIVERSITY	5600 CITY AVE	PHILADELPHIA	PA	19131	PHILADELPHIA	USA	Biomedical Research and Research Training	001	2	11/8/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$8,821
2023	2019	UNIVERSITY OF THE SCIENCES IN PHILADELPHIA	600 S 43RD ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Biomedical Research and Research Training	000	1	11/8/2022	NEW	-$8,821
2023	2019	ROWAN UNIVERSITY	201 MULLICA HILL RD RT 322	GLASSBORO	NJ	08028	GLOUCESTER	USA	Biomedical Research and Research Training	003	3	12/9/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$122,790
2023	2019	UNIVERSITY OF THE SCIENCES IN PHILADELPHIA	600 S 43RD ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Biomedical Research and Research Training	004	1	5/12/2023	NEW	$1
2023	2019	ST JOSEPH'S UNIVERSITY	5600 CITY AVE	PHILADELPHIA	PA	19131	PHILADELPHIA	USA	Biomedical Research and Research Training	002	2	12/9/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$122,954
														Subtotal = -$163

Issue Date FY: 2022 ( Subtotal = $1,676 )
2022	2019	UNIVERSITY OF THE SCIENCES IN PHILADELPHIA	600 S 43RD ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Biomedical Research and Research Training	000	1	6/30/2022	NEW	-$152,819
2022	2019	ST JOSEPH'S UNIVERSITY	5600 CITY AVE	PHILADELPHIA	PA	19131	PHILADELPHIA	USA	Biomedical Research and Research Training	001	2	7/1/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$154,495
														Subtotal = $1,676

Issue Date FY: 2019 ( Subtotal = $440,999 )
2019	2019	UNIVERSITY OF THE SCIENCES IN PHILADELPHIA	600 S 43RD ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Biomedical Research and Research Training	000	1	9/11/2019	NEW	$440,999
														Subtotal = $440,999

Grand Total All Awards = $381,206

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Characterizing the function and regulation of a conserved virulence-associated genetic pathway of pathogenic Alphaproteobacteria

Award Number: R15GM135933

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: 10/11/2022

PERIOD OF PERFORMANCE END DATE: 08/31/2023

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