Related Experiment Video
Updated: Aug 13, 2025
07:10
A Fluorescence-based Method to Study Bacterial Gene Regulation in Infected Tissues
Published on: February 19, 2019
9.1K
The Staphylococcus aureus protein IsdA increases SARS CoV-2 replication by modulating JAK-STAT signaling
Mariya I Goncheva1, Richard M Gibson2, Ainslie C Shouldice1
1Department of Microbiology and Immunology, University of Western Ontario, London, ON N6A 5C1, Canada.
Iscience
|January 23, 2023
Summary
Staphylococcus aureus enhances Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) replication by 10-fold. The bacterial protein IsdA alters host JAK-STAT signaling, increasing viral load during co-infection.
Area of Science:
- Virology
- Microbiology
- Immunology
Background:
- The COVID-19 pandemic caused by SARS-CoV-2 has led to millions of infections worldwide.
- Secondary bacterial co-infections, particularly with Staphylococcus aureus, complicate severe SARS-CoV-2 cases in about 25% of patients.
Purpose of the Study:
- To develop an in vitro co-infection model for examining viral and bacterial replication kinetics.
- To investigate the molecular mechanisms underlying Staphylococcus aureus-mediated enhancement of SARS-CoV-2 replication.
Main Methods:
- Development of an in vitro co-infection model.
- Analysis of viral and bacterial replication kinetics.
- Investigation of host-pathogen interactions and signaling pathways.
Main Results:
- SARS-CoV-2 infection did not affect bacterial interactions with host epithelial cells.
- Staphylococcus aureus significantly enhanced SARS-CoV-2 replication (10- to 15-fold).
- The bacterial protein IsdA was identified as responsible for this pro-viral effect by altering host JAK-STAT signaling (JAK2-STAT3).
Conclusions:
- Staphylococcus aureus actively promotes SARS-CoV-2 replication through its IsdA protein.
- IsdA modulates host transcription and JAK-STAT signaling, leading to increased viral replication.
- This study provides crucial insights into the complex interactions during SARS-CoV-2 and Staphylococcus aureus co-infection.
Related Concept Videos
01:20The JAK-STAT Signaling Pathway
9.1K
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...
9.1K
01:25cAMP-dependent Protein Kinase Pathways
6.5K
Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
6.5K
01:22Amplifying Signals via Enzymatic Cascade
8.6K
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
8.6K
01:22PI3K/mTOR/AKT Signaling Pathway
3.8K
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...
3.8K
01:19Interactions Between Signaling Pathways
6.4K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.4K
01:07MAPK Signaling Cascades
5.8K
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...
5.8K