Related Experiment Video

Updated: Jun 11, 2025

A Mouse Model to Assess Innate Immune Response to Staphylococcus aureus Infection
09:15

A Mouse Model to Assess Innate Immune Response to Staphylococcus aureus Infection

Published on: February 28, 2019

11.6K

TRPA1 Influences Staphylococcus aureus Skin Infection in Mice and Associates with HIF-1a and MAPK Pathway Modulation

Manoj Yadav1, Prem Prashant Chaudhary1, Grace Ratley1

  • 1Epithelial Therapeutic Unit, National Institute of Allergy, and Infectious Disease, National Institutes of Health, Bethesda, MD 20892, USA.

International Journal of Molecular Sciences
|September 28, 2024
PubMed

Insights

Targeting the TRPA1 ion channel offers a novel therapeutic strategy for methicillin-resistant Staphylococcus aureus (MRSA) infections. Inhibiting TRPA1 significantly reduces MRSA skin infection severity and abscess size in mice.

Area of Science:

  • Microbiology
  • Immunology
  • Pharmacology

Background:

  • Methicillin-resistant Staphylococcus aureus (MRSA) infections pose a significant public health challenge due to rising antibiotic resistance.
  • Novel therapeutic strategies are crucial for combating MRSA, including new antimicrobial agents and host defense modulation.
  • Transient Receptor Potential (TRP) ion channels TRPA1 and TRPV1 influence Staphylococcus aureus quorum sensing in vitro, but their in vivo roles in infection are unexplored.

Purpose of the Study:

  • To investigate the therapeutic potential of natural TRP ion channel inhibitors against MRSA skin infections in a mouse model.
  • To elucidate the molecular mechanisms underlying the effects of TRP ion channel inhibition on MRSA infection.

Main Methods:

  • Utilized a mouse model of MRSA skin infection, including TRPA1 and TRPV1 knockout mice.
  • Administered natural TRPA1 and TRPV1 inhibitors and assessed infection severity, abscess size, and inflammatory markers.
  • Performed tissue transcriptomic and metabolomic analyses, coupled with immunohistochemistry, to identify molecular pathways affected by TRPA1 inhibition.

Main Results:

  • TRPA1 knockout mice exhibited significantly reduced MRSA infection severity and abscess size compared to wild-type mice; TRPV1 deletion had no significant effect.
  • Treatment with natural TRPA1 inhibitors, with or without TRPV1 blockade, effectively reduced abscess size.
  • TRPA1 inhibition modulated heat shock protein expression, influenced HIF-1a and MAPK signaling pathways, decreased IL4 expression, and impacted purine and glycosaminoglycan metabolism.

Conclusions:

  • TRPA1 antagonism represents a promising, cost-effective therapeutic approach for mitigating MRSA infection severity.
  • TRPA1 inhibition impacts key host pathways, including heat shock protein expression and metabolic processes like diacylglycerol metabolism, offering a novel mechanism for infection control.
Keywords:
MRSATRPA1TRPV1metabolomicsstaphylococcus aureus

More Related Videos

Subcutaneous Infection of Methicillin Resistant Staphylococcus Aureus MRSA12:18

Subcutaneous Infection of Methicillin Resistant Staphylococcus Aureus MRSA

Published on: February 9, 2011

22.9K
An Adoptive Transfer Model of Rheumatoid Arthritis in Mice07:37

An Adoptive Transfer Model of Rheumatoid Arthritis in Mice

Published on: June 6, 2025

43

Related Concept Videos

MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.3K
T Cell Types and Functions01:24

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
959
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
3.4K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
8.7K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.8K