iScience
Volume 26, Issue 2, 17 February 2023, 105975
Journal home page for iScience

Article
The Staphylococcus aureus protein IsdA increases SARS CoV-2 replication by modulating JAK-STAT signaling

https://doi.org/10.1016/j.isci.2023.105975Get rights and content
Under a Creative Commons license
open access

Highlights

  • Established an in vitro SARS CoV-2-Staphylococcus aureus co-infection model

  • The S. aureus protein IsdA increases SARS CoV-2 replication

  • IsdA enhances the production of SARS CoV-2 infectious virus particles

  • IsdA manipulates host JAK-STAT signaling to the benefit of SARS CoV-2

Summary

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.

Subject areas

Biological sciences
Microbiology
Virology

Data and code availability

RNAseq reads have been deposited at GEO under accession number GSE218934 and are publicly available as of January 16th 2023. Accession numbers are listed in the key resources table. Additional supplemental items (Western blot images) are available from Mendeley data at https://data.mendeley.com/datasets/x4vr9vpmv7/1 (https://doi.org/10.17632/x4vr9vpmv7.1) and are also listed in the key resources table. This paper does not report original code. Any additional information required to reanalyse the data reported in this paper is available from the lead contact upon request.

Cited by (0)

3

Present address: Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC V8P 5C2, Canada

4

Lead contact