Comparison of Transcriptional Signatures of Three Staphylococcal Superantigenic Toxins in Human Melanocytes

Nabarun Chakraborty; Seshamalini Srinivasan; Ruoting Yang; Stacy-Ann Miller; Aarti Gautam; Leanne J. Detwiler; Bonnie C. Carney; Abdulnaser Alkhalil; Lauren T. Moffatt; Marti Jett; Jeffrey W. Shupp; Rasha Hammamieh

doi:10.3390/biomedicines10061402

Biomedicines (Jun 2022)

Comparison of Transcriptional Signatures of Three Staphylococcal Superantigenic Toxins in Human Melanocytes

Nabarun Chakraborty,
Seshamalini Srinivasan,
Ruoting Yang,
Stacy-Ann Miller,
Aarti Gautam,
Leanne J. Detwiler,
Bonnie C. Carney,
Abdulnaser Alkhalil,
Lauren T. Moffatt,
Marti Jett,
Jeffrey W. Shupp,
Rasha Hammamieh

Affiliations

Nabarun Chakraborty: Medical Readiness Systems Biology, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Seshamalini Srinivasan: Medical Readiness Systems Biology, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Ruoting Yang: Medical Readiness Systems Biology, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Stacy-Ann Miller: Medical Readiness Systems Biology, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Aarti Gautam: Medical Readiness Systems Biology, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Leanne J. Detwiler: Medical Readiness Systems Biology, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Bonnie C. Carney: Firefighters’ Burn and Surgical Research Laboratory, MedStar Health Research Institute, Washington, DC 20010, USA
Abdulnaser Alkhalil: Firefighters’ Burn and Surgical Research Laboratory, MedStar Health Research Institute, Washington, DC 20010, USA
Lauren T. Moffatt: Firefighters’ Burn and Surgical Research Laboratory, MedStar Health Research Institute, Washington, DC 20010, USA
Marti Jett: Medical Readiness Systems Biology, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Jeffrey W. Shupp: Firefighters’ Burn and Surgical Research Laboratory, MedStar Health Research Institute, Washington, DC 20010, USA
Rasha Hammamieh: Medical Readiness Systems Biology, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA

DOI: https://doi.org/10.3390/biomedicines10061402
Journal volume & issue: Vol. 10, no. 6
p. 1402

Abstract

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Staphylococcus aureus, a gram-positive bacterium, causes toxic shock through the production of superantigenic toxins (sAgs) known as Staphylococcal enterotoxins (SE), serotypes A-J (SEA, SEB, etc.), and toxic shock syndrome toxin-1 (TSST-1). The chronology of host transcriptomic events that characterizes the response to the pathogenesis of superantigenic toxicity remains uncertain. The focus of this study was to elucidate time-resolved host responses to three toxins of the superantigenic family, namely SEA, SEB, and TSST-1. Due to the evolving critical role of melanocytes in the host’s immune response against environmental harmful elements, we investigated herein the transcriptomic responses of melanocytes after treatment with 200 ng/mL of SEA, SEB, or TSST-1 for 0.5, 2, 6, 12, 24, or 48 h. Functional analysis indicated that each of these three toxins induced a specific transcriptional pattern. In particular, the time-resolved transcriptional modulations due to SEB exposure were very distinct from those induced by SEA and TSST-1. The three superantigens share some similarities in the mechanisms underlying apoptosis, innate immunity, and other biological processes. Superantigen-specific signatures were determined for the functional dynamics related to necrosis, cytokine production, and acute-phase response. These differentially regulated networks can be targeted for therapeutic intervention and marked as the distinguishing factors for the three sAgs.

Published in Biomedicines

ISSN: 2227-9059 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Biology (General)
Website: http://www.mdpi.com/journal/biomedicines

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