Altering the infection environment for the eradication of S. aureus infection
NIAID - National Institute of Allergy and Infectious Diseases
About This Grant
Abstract Skin and soft tissue infections (SSTIs) are a leading cause of emergency department visits, with community- acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) as the predominant pathogen. SSTIs often present as abscesses and can progress to life-threatening infections such as osteomyelitis, sepsis, and endocarditis. Rising antibiotic resistance has complicated treatment, with frequent recurrence despite therapy. This highlights the need for adjunctive strategies to enhance antibiotic efficacy, particularly through targeted immune modulation. While the immune response can both support and hinder antibiotic activity, the mechanisms underlying these effects in SSTIs remain poorly defined. Our central hypothesis is that distinct phases of the host immune response differentially influence MRSA susceptibility to antibiotics. In Aim 1, we will investigate how neutrophils enriched in the inflammatory phase of SSTIs, promote antibiotic tolerance. We show that human neutrophils induce robust tolerance in S. aureus in vitro, and that neutropenia improves vancomycin efficacy in vivo. In Aim 2, we will test whether enhancing the transition to the resolution phase using PPARγ agonists promotes antibiotic susceptibility. We will explore how resolution-phase effectors—polyamines and monounsaturated fatty acids (MUFAs)—synergize with antibiotics to clear infection. Our preliminary data show that USA300 isolates are uniquely resistant to spermine but remain sensitive to other polyamines and MUFAs, which enhance vancomycin activity. In Aim 3, we will determine how immune dysfunction in diabetic infections contributes to antibiotic failure and emergence of resistance. We find that diabetic SSTIs are marked by impaired oxidative burst due to defective mTOR- dependent GLUT-1 expression in phagocytes. This dysfunction blocks progression to the resolution phase, impairing production of bactericidal polyamines and MUFAs. Completion of this proposal will identify host immune processes that induce antibiotic tolerance or augment antimicrobial efficacy. By targeting these pathways with immune modulators such as PPARγ and mTOR agonists, we aim to develop novel adjunctive therapies to improve outcomes in MRSA SSTIs, including those complicated by diabetes or antimicrobial resistance.
Grant Summary
Altering the infection environment for the eradication of S. aureus infection is a NIAID - National Institute of Allergy and Infectious Diseases grant providing up to $3.1M for university, nonprofit, healthcare org. Applications are due 2030-06-30 (open). Check eligibility and apply with FindGrants.
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How to Apply
Up to $3.1M
2030-06-30
- 1Confirm your organization is eligible for Altering the infection environment for the eradication of S. aureus infection from NIAID - National Institute of Allergy and Infectious Diseases, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
- 4Review every section against the requirements checklist, then export a submission-ready application pack and submit it to NIAID - National Institute of Allergy and Infectious Diseases before the deadline.
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Altering the infection environment for the eradication of S. aureus infection: Frequently Asked Questions
Who is eligible for the Altering the infection environment for the eradication of S. aureus infection?
Altering the infection environment for the eradication of S. aureus infection is offered by NIAID - National Institute of Allergy and Infectious Diseases and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the Altering the infection environment for the eradication of S. aureus infection provide?
Altering the infection environment for the eradication of S. aureus infection provides up to $3.1M per award from NIAID - National Institute of Allergy and Infectious Diseases. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the Altering the infection environment for the eradication of S. aureus infection deadline?
Applications for Altering the infection environment for the eradication of S. aureus infection are due 2030-06-30 (open). Because deadlines can change, verify the date with the funder, NIAID - National Institute of Allergy and Infectious Diseases, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Altering the infection environment for the eradication of S. aureus infection?
To apply for Altering the infection environment for the eradication of S. aureus infection, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NIAID - National Institute of Allergy and Infectious Diseases.