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

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

doi:10.3390/biomedicines10061402

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

Nabarun Chakraborty

^1,*,†,

Seshamalini Srinivasan

^1,2,†,

¹,

¹,

¹,

^1,2,

^3,4,5

³,

^3,4,5,

¹,

^3,4,5,6 and

Medical Readiness Systems Biology, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA

The Geneva Foundation, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA

Firefighters’ Burn and Surgical Research Laboratory, MedStar Health Research Institute, Washington, DC 20010, USA

⁴

Department of Surgery, Georgetown University School of Medicine, Washington, DC 20057, USA

⁵

Department of Biochemistry and Molecular & Cellular Biology, Georgetown University School of Medicine, Washington, DC 20057, USA

⁶

The Burn Center, MedStar Washington Hospital Center, Washington, DC 20010, USA

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Academic Editor: Marianna Christodoulou

Biomedicines 2022, 10(6), 1402; https://doi.org/10.3390/biomedicines10061402

Received: 20 April 2022 / Revised: 4 May 2022 / Accepted: 6 May 2022 / Published: 14 June 2022

(This article belongs to the Special Issue Omics Approaches to Immune-Mediated Inflammatory Diseases: Towards Novel Biomarkers and Potential Therapeutic Targets)

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Abstract

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. View Full-Text

Keywords: superantigens; gene expression; transcriptional dynamics; staphylococcal enterotoxins; SEB; SEA; TSST-1; toxins; biological networks; clustering; functional pathways; time–course analysis; cDNA microarray; human melanocytes

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MDPI and ACS Style

Chakraborty, N.; Srinivasan, S.; Yang, R.; Miller, S.-A.; Gautam, A.; Detwiler, L.J.; Carney, B.C.; Alkhalil, A.; Moffatt, L.T.; Jett, M.; Shupp, J.W.; Hammamieh, R. Comparison of Transcriptional Signatures of Three Staphylococcal Superantigenic Toxins in Human Melanocytes. Biomedicines 2022, 10, 1402. https://doi.org/10.3390/biomedicines10061402

AMA Style

Chakraborty N, Srinivasan S, Yang R, Miller S-A, Gautam A, Detwiler LJ, Carney BC, Alkhalil A, Moffatt LT, Jett M, Shupp JW, Hammamieh R. Comparison of Transcriptional Signatures of Three Staphylococcal Superantigenic Toxins in Human Melanocytes. Biomedicines. 2022; 10(6):1402. https://doi.org/10.3390/biomedicines10061402

Chicago/Turabian Style

Chakraborty, Nabarun, 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, and Rasha Hammamieh. 2022. "Comparison of Transcriptional Signatures of Three Staphylococcal Superantigenic Toxins in Human Melanocytes" Biomedicines 10, no. 6: 1402. https://doi.org/10.3390/biomedicines10061402

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

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