Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Characterization of the Staphylococcus aureus fatty acid degradation pathway

Award Number: F31AI181362
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 09/01/2024
PERIOD OF PERFORMANCE END DATE: 08/31/2028

Group Awards By:

View Award Description

Characterization of the Staphylococcus aureus fatty acid degradation pathway - PROJECT SUMMARY/ABSTRACT Bacteria require fatty acids for a variety of biological functions, including the construction of phospholipids. Staphylococcus aureus, like other bacteria, synthesize fatty acids using a fatty acid biosynthesis pathway referred to as FASII, but can also scavenge fatty acids from the environment using the recently described fatty acid kinase (Fak) pathway. In addition to fatty acid biosynthesis and acquisition, it is common for bacteria to degrade fatty acids using fatty acid degradation (Fad) enzymes. Bacteria can degrade fatty acids for energy production (known as b-oxidation) but can also degrade fatty acids to alter the length of the acyl chain. S. aureus has been thought to not possess the capacity to degrade or perform b-oxidation of fatty acids. This is due, in part, to the absence of a key crotonase enzyme. This is surprising considering that S. aureus is annotated to encode all the other necessary Fad enzymes, though their function has not been confirmed. During RNAseq studies of the Fak pathway, we observed an ~17-fold increased expression of the group of genes annotated to encode Fad proteins when the Fak pathway was inactivated. Indeed, no crotonase enzyme was apparent, though all the other Fad functionalities were annotated. Using bioinformatics, we identified a putative crotonase enzyme in S. aureus that we now call FadB based on nomenclature in other systems. When co-expressed with S. aureus FadA, FadB can functionally complement an E. coli fadA and fadB mutants on minimal media with fatty acid as a sole carbon source. This demonstrates that 1) S. aureus FadB can substitute for the E. coli crotonase activity-containing enzyme, and 2) S. aureus does possess a complete Fad pathway and likely can degrade fatty acids. We seek to characterize the regulation of this pathway, demonstrate the saFadA and saFadB proteins form a complex like the E. coli proteins, and demonstrate the functionality of the S. aureus Fad pathway in three Specific Aims. Aim 1 will identify regulatory proteins of the Fad operon. Aim 2 determines if the S. aureus FadA and FadB proteins form a complex. In addition, Aim 3 examines the ability for S. aureus to degrade fatty acids and use them as alternative carbon sources using controlled expression of the Fad genes using a combination of 13C- labeled fatty acids with mass spectrometry and growth assays. The Fad-encoding genes have been identified in a variety of transcriptomic studies but have remained unstudied. This is likely due to the known dogma in the field that S. aureus does not possess a complete Fad pathway and cannot degrade fatty acids. We anticipate that the completion of this application will redefine fatty acid metabolism in S. aureus and determine for the first time that S. aureus can degrade fatty acids. This will change how the field understands S. aureus metabolism and will set the stage for future applications examining the role of this pathway in cell physiology and pathogenesis.


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 = $37,460 )
2025	2025	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE, INC.	3901 RAINBOW BLVD	KANSAS CITY	KS	66160	WYANDOTTE	USA	Allergy and Infectious Diseases Research	000	2	7/29/2025	NON-COMPETING CONTINUATION	$37,460
														Subtotal = $37,460

Issue Date FY: 2024 ( Subtotal = $37,460 )
2024	2024	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE, INC.	3901 RAINBOW BLVD	KANSAS CITY	KS	66160	WYANDOTTE	USA	Allergy and Infectious Diseases Research	001	1	8/26/2024	NEW	$0
2024	2024	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE, INC.	3901 RAINBOW BLVD	KANSAS CITY	KS	66160	WYANDOTTE	USA	Allergy and Infectious Diseases Research	000	1	8/5/2024	NEW	$37,460
														Subtotal = $37,460

Grand Total All Awards = $74,920

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Characterization of the Staphylococcus aureus fatty acid degradation pathway

Award Number: F31AI181362

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 09/01/2024

PERIOD OF PERFORMANCE END DATE: 08/31/2028

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer