Staphylococcal Secretome Profile Associated with Increased Clinical Severity in Cutaneous T-cell Lymphoma Clinical Isolates Restricted; Files Only

Abstract

Staphylococcus aureus is an established colonizer in Cutaneous T-Cell Lymphoma (CTCL) patients. S. aureus pathogenesis is mediated by secreted toxins (secretome), including hemolysins, proteases, and superantigens linked to immune evasion and malignant progression. Black CTCL patients experience more than twice the rate of invasive infections with S. aureus, yet the role of the S. aureus secretome in health disparities has not been studied. Patients consented to a prospective biobanking protocol and underwent standardized skin swabbing to generate a CTCL clinical isolate bank. Hemolysis assays were performed using rabbit blood agar to quantify hemolysin activity. Proteomic analyses focused on samples grown in the post-exponential growth stage to detect the presence of 𝛼-hemolysin, δ-hemolysin, PSM𝛼1, PSM𝛼2, PSM𝛼3, PSM𝛼4, and V8 protease using liquid chromatography-mass spectrometry. An initial cohort of 41 patients, yielded 253 S. aureus stocks from clinical isolates (148 from Black patients and 105 from White patients). Disease severity parameters were determined by stratified mSWAT quartiles. In the most severe mSWAT quartile, isolates from Black patients (mSWAT score >98.5, n=47) exhibited significantly greater hemolytic activity than those from White patients (mSWAT score >80.5, n=22) (p=0.0256). Additionally, isolates from Black patients with tumor-stage disease (T3) had significantly greater hemolytic activity than non-tumor stages (T1, T2, and T4) (p<0.05). Initial proteomics ratios reveal Black severe patients having similar virulence abundance to a known highly virulent S. aureus MRSA strain, while White severe patients have potentially fewer to no virulence factors expressed. However, proteomic analyses are ongoing to further characterize additional toxins in the secretome and identify virulence factors associated with severity and race. This study represents an early comparative analysis of the S. aureus secretome in CTCL using a racially diverse patient cohort. Integrating functional and proteomic approaches may clarify microbial contributions to CTCL progression and provide insight into biological mechanisms contributing to racial disparities in disease severity.

Table of Contents

Purpose

 

Chapter 1: Introduction                                          

-      Cutaneous T-cell Lymphoma

-      Staphylococcus aureus

-      Staphylococcus aureus secretome

-             Hemolysin

-             Phenol-Soluble Modulins

-             V8 Protease

-      Project Aims and Research Questions

Chapter 2: Materials and Methods

-      Biospecimen collection

-      Generation of the CTCL Clinical Isolate Bank

-      Hemolysis: Hemolysis Assays

-      Hemolysis: Hemolysis Analysis

-      Proteomics: Secretome Harvest

-      Proteomics: Protein Digest

-      Proteomics: Liquid Chromatography and Mass Spectrometry

-      Proteomics: Liquid Chromatography and Mass Spectrometry Data Analysis

Chapter 3: Results

-      Summary of CTCL clinical isolate glycerol stocks used in study

-      Comparison of hemolytic activity between Staphylococcus aureus and non-aureus Staphylococcus Isolates

-      Comparison of hemolytic activity between lesional and non-lesional isolates

-      Comparison of mSWAT distribution and race

-      Comparison of hemolytic activity between Black and White patients

-      Comparison of hemolytic activity among Staphylococcus aureus isolates stratified by CTCL disease severity

-      Comparison of hemolytic activity among Staphylococcus aureus isolates stratified by Tumor stage

-      Comparison of secreted virulence abundance in S. aureus isolates from CTCL patients

Chapter 4: Discussion

Chapter 5: Conclusion

Chapter 6: References

Chapter 7: Table and Figure Legend

About this Honors Thesis

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School	Emory College
Department	Biology
Degree	B.S.
Submission	Honors Thesis
Language	English
Research Field	Biology, Microbiology
Keyword	Cutaneous T-cell lymphoma Virulence factors Hemolysis Staphylococcus aureus
Committee Chair / Thesis Advisor	Cassandra Quave, Emory University
Committee Members	Pamela Allen, Emory University Brandon Berryhill, Emory University Bruce Levin, Emory University

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