Summary of Study ST003483

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002139. The data can be accessed directly via it's Project DOI: 10.21228/M84F91 This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

Study ID	ST003483
Study Title	Tissue niche influences immune and metabolic profiles to Staphylococcus aureus biofilm infection (Extracellular data)
Study Summary	Infection is a devastating post-surgical complication, often requiring additional procedures and prolonged antibiotic therapy. This is especially relevant for craniotomy and prosthetic joint infections (PJI), both of which are characterized by biofilm formation on the bone or implant surface, respectively, with S. aureus representing a primary cause. The local tissue microenvironment likely has profound effects on immune attributes that can influence treatment efficacy, which becomes critical to consider when developing therapeutics for biofilm infections. However, the extent to which distinct tissue niches influence immune function during biofilm development remains relatively unknown. To address this, we compare the metabolomic, transcriptomic, and functional attributes of leukocytes in mouse models of S. aureus craniotomy and PJI complemented with patient samples from both infection modalities, which reveals profound tissue niche-dependent differences in nucleic acid, amino acid, and lipid metabolism with links to immune modulation. These signatures are both spatially and temporally distinct, differing not only between infection sites but evolving over time within a single model. Collectively, this demonstrates that biofilms elicit unique immune and metabolic responses that are heavily influenced by the local tissue microenvironment, which will likely have important implications when designing therapeutic approaches targeting these infections. This submission contains the extracellular metabolomic data for the larger project.
Institute	University of Nebraska Medical Center
Department	Department of pathology, microbiology and immunology
Last Name	Shinde
First Name	Dhananjay
Address	DRC 2, 7066, UNMC, Emily st
Email	dhananjay.shinde@unmc.edu
Phone	4025597623
Submit Date	2024-09-14
Raw Data Available	Yes
Raw Data File Type(s)	mzXML
Analysis Type Detail	LC-MS
Release Date	2024-09-24
Release Version	1

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Treatment:

Treatment ID:	TR003620
Treatment Summary:	All mice were group-housed at 21-23°C (22°C average) and 30-70% humidity (55% average) under 12 h light/dark cycle with free access to food (2019S Teklad Global 19% Protein Extruded Rodent Diet; Inotiv, West Lafayette, IN) and water. S. aureus craniotomy infection was established in male and female 8- to 10-week-old C57BL/6J mice (RRID:IMSR_JAX:000664). Briefly, ketamine and xylazine were administered to achieve a surgical plane of anesthesia before skin disinfection with betadine. A midline incision of the scalp was made, whereupon a bone flap was created using a high-speed pneumatic drill (Stryker Corporation, Kalamazoo, MI). The bone flap was incubated with 0.5 mL of S. aureus USA300 LAC13C diluted to 10^6/mL in brain-heart infusion broth at 37°C for 5 min and subsequently rinsed in PBS, blotted dry on a sterile field, and reimplanted. This procedure reliably produces an infectious inoculum of 10^3 CFUs per bone flap, which more accurately models surgical site infection that progresses to biofilm formation. The scalp incision was closed using 6-0 nylon suture and animals were continuously monitored until they regained ambulation, and daily thereafter. S. aureus PJI was established in male and female 8- to 10-week-old C57BL/6J mice. Mice were anesthetized with ketamine and xylazine prior to skin disinfection with betadine and initial incision of the quadriceps. A secondary incision was made to laterally displace the patellar tendon and a burr hole was created in the distal end of the femur with a 26-gauge needle. An orthopedic-grade nickel-titanium Kirschner wire (0.6 mm diameter; Custom Wire Technologies, Port Washington, WI) was inserted through the burr hole into the medullary canal and 10^3 CFUs of S. aureus USA300 LAC13C were inoculated at the tip of the wire and the incision was closed with nylon suture. Mice received buprenorphine SR to alleviate any post-surgical pain and were continuously monitored until ambulatory and daily thereafter.

Treatment ID:

TR003620

Treatment Summary:

All mice were group-housed at 21-23°C (22°C average) and 30-70% humidity (55% average) under 12 h light/dark cycle with free access to food (2019S Teklad Global 19% Protein Extruded Rodent Diet; Inotiv, West Lafayette, IN) and water. S. aureus craniotomy infection was established in male and female 8- to 10-week-old C57BL/6J mice (RRID:IMSR_JAX:000664). Briefly, ketamine and xylazine were administered to achieve a surgical plane of anesthesia before skin disinfection with betadine. A midline incision of the scalp was made, whereupon a bone flap was created using a high-speed pneumatic drill (Stryker Corporation, Kalamazoo, MI). The bone flap was incubated with 0.5 mL of S. aureus USA300 LAC13C diluted to 10^6/mL in brain-heart infusion broth at 37°C for 5 min and subsequently rinsed in PBS, blotted dry on a sterile field, and reimplanted. This procedure reliably produces an infectious inoculum of 10^3 CFUs per bone flap, which more accurately models surgical site infection that progresses to biofilm formation. The scalp incision was closed using 6-0 nylon suture and animals were continuously monitored until they regained ambulation, and daily thereafter. S. aureus PJI was established in male and female 8- to 10-week-old C57BL/6J mice. Mice were anesthetized with ketamine and xylazine prior to skin disinfection with betadine and initial incision of the quadriceps. A secondary incision was made to laterally displace the patellar tendon and a burr hole was created in the distal end of the femur with a 26-gauge needle. An orthopedic-grade nickel-titanium Kirschner wire (0.6 mm diameter; Custom Wire Technologies, Port Washington, WI) was inserted through the burr hole into the medullary canal and 10^3 CFUs of S. aureus USA300 LAC13C were inoculated at the tip of the wire and the incision was closed with nylon suture. Mice received buprenorphine SR to alleviate any post-surgical pain and were continuously monitored until ambulatory and daily thereafter.