Related Experiment Video
Updated: Aug 13, 2025
A Fluorescence-based Method to Study Bacterial Gene Regulation in Infected Tissues
Published on: February 19, 2019
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.
Abstract:
The Severe Acute Respiratory Syndrome Coronavirus 2 (CoV-2) pandemic has affected millions globally. A significant complication of CoV-2 infection is secondary bacterial co-infection, as seen in approximately 25% of severe cases. The most common organism isolated during co-infection is Staphylococcus aureus. Here, we describe the development of an in vitro co-infection model where both viral and bacterial replication kinetics may be examined. We demonstrate CoV-2 infection does not alter bacterial interactions with host epithelial cells. In contrast, S. aureus enhances CoV-2 replication by 10- to 15-fold. We identify this pro-viral activity is due to the S. aureus iron-regulated surface determinant A (IsdA) protein and demonstrate IsdA modifies host transcription. We find that IsdA alters Janus Kinase - Signal Transducer and Activator of Transcription (JAK-STAT) signaling, by affecting JAK2-STAT3 levels, ultimately leading to increased viral replication. These findings provide key insight into the molecular interactions between host cells, CoV-2 and S. aureus during co-infection.
Insights
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
01:25cAMP-dependent Protein Kinase Pathways
01:22Amplifying Signals via Enzymatic Cascade
01:22PI3K/mTOR/AKT Signaling Pathway
01:19Interactions Between Signaling Pathways
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...
01:07MAPK Signaling Cascades