Related Experiment Video

Updated: May 23, 2026

Visualization of Inflammatory Caspases Induced Proximity in Human Monocyte-Derived Macrophages
08:41

Visualization of Inflammatory Caspases Induced Proximity in Human Monocyte-Derived Macrophages

Published on: April 6, 2022

Staphylococcus aureus activation of caspase 1/calpain signaling mediates invasion through human keratinocytes

Grace Soong1, Jarin Chun, Dane Parker

  • 1Department of Pediatrics, Columbia University, New York, New York 10032, USA.

The Journal of Infectious Diseases
|March 30, 2012
PubMed

Insights

Staphylococcus aureus uses pyroptosis, a form of inflammatory cell death, to invade skin cells. Inhibiting specific cell death pathways or alpha-hemolysin may prevent invasive skin infections.

Area of Science:

  • Microbiology
  • Immunology
  • Dermatology

Background:

  • USA300 Staphylococcus aureus causes significant skin and soft tissue infections.
  • Virulence factors like protein A and alpha-hemolysin (Hla) contribute to invasive disease by activating host signaling.
  • Host cell inflammatory responses are crucial in staphylococcal pathogenesis.

Purpose of the Study:

  • To investigate the role of keratinocyte pyroptosis in Staphylococcus aureus invasion.
  • To identify the mechanisms by which S. aureus induces keratinocyte cell death and penetration.
  • To explore potential therapeutic targets for invasive staphylococcal skin infections.

Main Methods:

  • Utilized human keratinocyte models to study S. aureus USA300 invasion.
  • Investigated the activation of pyroptosis (caspase 1-dependent cell death) and necrosis.
  • Assessed the role of alpha-hemolysin (Hla), protein A, and Panton-Valentine leukocidin in invasion.
  • Examined the function of calpains, Ca(2+)-dependent proteases, and their inhibitor calpastatin.
  • Tested the efficacy of inhibiting calpain or caspase 1 activity on staphylococcal invasion.

Main Results:

  • S. aureus exploits keratinocyte pyroptosis, a caspase 1-dependent inflammatory cell death, for invasion.
  • Alpha-hemolysin (Hla) targets calpastatin, the inhibitor of calpains, leading to keratinocyte necrosis.
  • Neither Panton-Valentine leukocidin nor protein A were essential for invasion in this model.
  • Inhibition of calpain or caspase 1 activity effectively prevented S. aureus invasion across keratinocytes.

Conclusions:

  • Staphylococcus aureus utilizes keratinocyte pyroptosis and Hla-mediated necrosis to facilitate invasion.
  • Targeting calpain or caspase 1 pathways offers a potential strategy to block staphylococcal skin invasion.
  • Interfering with Hla or specific keratinocyte signaling cascades may prevent invasive skin infections.

More Related Videos

Evaluation of Caspase Activation to Assess Innate Immune Cell Death10:23

Evaluation of Caspase Activation to Assess Innate Immune Cell Death

Published on: January 20, 2023

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation08:47

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation

Published on: March 5, 2018

Related Concept Videos

Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.
Staphylococcal Skin Infections01:29

Staphylococcal Skin Infections

Staphylococcus aureus is a Gram-positive coccus that resides harmlessly on the skin and mucous membranes of healthy individuals. When the skin barrier is breached, it can shift from a commensal to an opportunistic pathogen. This transition is facilitated by surface adhesins, such as clumping factor B and S. aureus surface protein G (SasG), which bind to structural proteins, including loricrin and cytokeratin, in the damaged epidermis. Protein A, another key factor, binds the Fc region of...
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
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...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Cancer Cell Migration through Invadopodia01:35

Cancer Cell Migration through Invadopodia

Invadosome is a broad category of cell surface structures with proteolytic activity that  degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However, invadopodia can...