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Assistant Professor of Microbiology
Office: 3-450 Bowen Science Building51 Newton RdIowa City, IA 52242
Office Phone: 319-335-7790
Lab: 3-401 Bowen Science Building51 Newton RdIowa City, IA 52242
Email: firstname.lastname@example.orgWeb: Salgado-Pabón Lab Website
BS, Medical Microbiology and Immunology, University of Wisconsin-MadisonMS, Medical Microbiology and Immunology, University of Wisconsin-MadisonPhD, Microbiology, University of Wisconsin-Madison
Post Doctoral, Cell Biology and Infection, Institut PasteurPost Doctoral, Microbiology, University of Iowa
Biosciences Graduate Program
Staphylococcus aureus is the leading cause of serious infectious diseases, resulting in more fatalities in the U.S. than even AIDS. Contributing to these infections are both healthcare and community-associated, methicillin-susceptible and resistant S. aureus, corresponding largely to the USA100 to USA400 clonal types. We study diseases caused by strains of all four major clonal groups in highly sensitive rabbit models of infective endocarditis, sepsis, and pneumonia. A promising area of research for understanding and combatting S. aureus infections is the study of staphylococcal enterotoxins (SEs) also known as superantigens (SAgs). SAgs are major secreted virulence factors of S. aureus. It has been known for decades that these molecules cause vomiting and diarrhea (hence the name enterotoxin) but are also highly lethal in humans. Almost every S. aureus strain encodes for and can produce SAgs when the opportunity arises. It has become evident over the past years that SAgs are critical contributors to the pathophysiology of the life-threatening illnesses that S. aureus causes, including septicemia, endocarditis (which leads to fulminant heart infections), necrotizing and hemorrhagic pneumonias (including secondary bacterial pneumonia), and chronic skin infections (including diabetic foot ulcers). Most of these illnesses carry high mortality rates, even with current available treatments.
Superantigen Mechanism in Infective Endocarditis
Infective endocarditis, which occurs in 30-60% of patients with S. aureus bacteremia, is an infection of the heart endothelium, predominantly valves, that results in the formation of large vegetative lesions composed of host factors and bacterial aggregates. Vegetations often lead to congestive heart failure and systemic embolization, resulting in strokes, metastatic abscesses, persistent bacteremia, and toxic shock syndrome (TSS). Over the past decades, infective endocarditis outcomes have not improved (mortality rates are still 40-50%), and infection rates are steadily increasing. We have shown that highly produced SAgs (as TSST-1 and SEC) are critical for vegetation formation. We are currently defining the underlying mechanism of superantigen involvement.
Superantigen Mechanism of Adaptive Immune Suppression
SAgs crosslink the Vβ chain of the T cell receptor (TCR) to the HLA class II molecule on antigen presenting cells, inducing massive activation of both T cells and macrophages with the concomitant production of cytokines. SAgs are known for causing TSS. However, it is clear that SAgs are also causative or associated with other S. aureus life-threatening infections. Remarkably, 20% of people in the U.S. do not develop antibodies to any given SAg, remaining susceptible to SAg-associated diseases over their lifetime. T cell exhaustion is the most common explanation used to account for T and B cell unresponsiveness during TSS. However, T cell exhaustion has not been observed in humans or rabbits with TSS. We are investigating the cellular and molecular mechanism underlying SAg-induced immune suppression.
Superantigen Enhancement of Endotoxin Shock
Endotoxemia occurs in humans during TSS and in rabbits injected with TSST-1. An interesting and potentially important property of SAgs is their ability to enhance the lethality of lipopolysaccharide (LPS) by up to a million fold. Furthermore, the susceptibility of humans and rabbits to SAgs correlates with the presence of gram-negative rods bearing toxic LPS colonizing the intestinal and vaginal tracts. Superantigen-induced LPS enhancement results from impaired LPS clearance by the liver. We are elucidating the mechanism of LPS and superantigen synergism in in vitro and in vivo systems.
Center for Immunology and Immune-based Diseases
Molecular analysis of staphylococcal superantigens.
Methods Mol Biol.
Vaccination Against Staphylococcus aureus Pneumonia.
J Infect Dis.
2014. Epub ahead of print.
The Staphylococcus aureus ArlRS Two-Component System Is a Novel Regulator of Agglutination and Pathogenesis.
2013 December. 9(12):e1003819.
Menaquinone analogs inhibit growth of bacterial pathogens.
Antimicrob Agents Chemother.
2013 November. 57(11):5432-7.
Superantigens are critical for Staphylococcus aureus Infective endocarditis, sepsis, and acute kidney injury.
2013 August 20. 4(4):e00494-13.
Staphylococcal and streptococcal superantigen exotoxins.
Clin Microbiol Rev.
2013 July. 26(3):422-47.
Enterococcus faecalis inhibits superantigen toxic shock syndrome toxin-1-induced interleukin-8 from human vaginal epithelial cells through tetramic acids.
2013 April 22. 8(4):e61255.
Shigella impairs T lymphocyte dynamics in vivo.
Proc Natl Acad Sci USA.
2013 March 19. 110(12):4458-63.
di Bartolo V,
The Shigella flexneri type three secretion system effector IpgD inhibits T cell migration by manipulating host phosphoinositide metabolism.
Cell Host Microbe.
2011 April 21. 9(4):263-72.
Di Santo J,
Th17 cells are the dominant T cell subtype primed by Shigella flexneri mediating protective immunity.
2010 February 15. 184(4):2076-85.
Date Last Modified: 02/07/2014 -
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