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

Mariya I Goncheva; Richard M Gibson; Ainslie C Shouldice; Jimmy D Dikeakos; David E Heinrichs

doi:10.1016/j.isci.2023.105975

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

iScience. 2023 Feb 17;26(2):105975. doi: 10.1016/j.isci.2023.105975. Epub 2023 Jan 13.

Authors

Mariya I Goncheva¹, Richard M Gibson², Ainslie C Shouldice¹, Jimmy D Dikeakos¹, David E Heinrichs¹

Affiliations

¹ Department of Microbiology and Immunology, University of Western Ontario, London, ON N6A 5C1, Canada.
² ImPaKT Laboratory, Schulich School of Medicine and Dentistry, 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.

Keywords: Biological sciences; Microbiology; Virology.