Wilmara Salgado-Pabón, PhD

Portrait
Assistant Professor of Microbiology and Immunology

Contact Information

Office
3-450 Bowen Science Building
51 Newton Rd
Iowa City, IA 52242
319-335-7790

Lab
3-401 Bowen Science Building
51 Newton Rd
Iowa City, IA 52242
319-335-7817

Education

BS, Microbiology and Immunology, University of Wisconsin-Madison
MS, Microbiology and Immunology, University of Wisconsin-Madison
PhD, Microbiology and Immunology, University of Wisconsin-Madison
Postdoctoral Fellow, Cell Biology and Infection, Institut Pasteur
Postdoctoral Fellow, Microbiology, University of Iowa

Education/Training Program Affiliations

Biomedical Science Program

Center, Program and Institute Affiliations

Center for Immunology and Immune-based Diseases

Research Summary

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 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.

Publications

Kulhankova, K., Kinney, K. J., Stach, J. M., Gourronc, F. A., Grumbach, I. M., Klingelhutz, A. J. & Salgado-Pabón, W. (2017). The Superantigen Toxic Shock Syndrome Toxin-1 Alters Human Aortic Endothelial Cell Function. Infection and Immunity. PMID: 29229737.

Herrera, A., Kulhankova, K., Sonkar, V. K., Dayal, S., Klingelhutz, A. J., Salgado-Pabón, W. & Schlievert, P. M. (2017). Staphylococcal ß-Toxin Modulates Human Aortic Endothelial Cell and Platelet Function through Sphingomyelinase and Biofilm Ligase Activities. MBio, 8(2), e00273-17. PMID: 28325766.

Paharik, A. E., Salgado-Pabón, W., Meyerholz, D. K., White, M. J., Schlievert, P. M. & Horswill, A. R. (2016). The Spl Serine Proteases Modulate Staphylococcus aureus Protein Production and Virulence in a Rabbit Model of Pneumonia. mSphere, 1(5), e00208-16. PMID: 27747296.

King, J. M., Kulhankova, K., Stach, C. S., Vu, B. G. & Salgado-Pabón, W. (2016). Phenotypes and Virulence among Staphylococcus aureus USA100, USA200, USA300, USA400, and USA600 Clonal Lineages. mSphere, 1(3), e00071-16. PMID: 27303750.

Crosby, H. A., Schlievert, P. M., Merriman, J. A., King, J. M., Salgado-Pabón, W. & Horswill, A. R. (2016). The Staphylococcus aureus Global Regulator MgrA Modulates Clumping and Virulence by Controlling Surface Protein Expression. PLoS Pathog, 12(5), e1005604. PMID: 27144398.

Herrera, A., Vu, B. G., Stach, C. S., Merriman, J. A., Horswill, A. R., Salgado-Pabón, W. & Schlievert, P. M. (2016). Staphylococcus aureus ß-Toxin Mutants Are Defective in Biofilm Ligase and Sphingomyelinase Activity, and Causation of Infective Endocarditis and Sepsis. Biochemistry, 55(17), 2510-7. PMID: 27015018.

Stach, C. S., Vu, B. G., Merriman, J. A., Herrera, A., Cahill, M. P., Schlievert, P. M. & Salgado-Pabón, W. (2016). Novel Tissue Level Effects of the Staphylococcus aureus Enterotoxin Gene Cluster Are Essential for Infective Endocarditis. PLoS One, 11(4), e0154762. PMID: 27124393.

Salgado-Pabón, W., Schlievert, P. M. (2016). Aortic Valve Damage for the Study of Left-Sided, Native Valve Infective Endocarditis in Rabbits. pp. 73-80. Methods Mol Biol. PMID: 26676038.

Schlievert, P. M., Salgado-Pabón, W., Herrera, A., Vu, B. G., Stach, C. S. & Merriman, J. A. (2015). Reply to Dupieux et al. on "Does ß-toxin production contribute to the cytotoxicity of hypervirulent Staphylococcus aureus?". (Vols. 211). (5), pp. 847-8. J Infect Dis. PMID: 25180237.

Vu, B. G., Stach, C. S., Kulhankova, K., Salgado-Pabón, W., Klingelhutz, A. J. & Schlievert, P. M. (2015). Chronic superantigen exposure induces systemic inflammation, elevated bloodstream endotoxin, and abnormal glucose tolerance in rabbits: possible role in diabetes. MBio, 6(2), e02554. PMID: 25714716.

Schlievert, P. M., Salgado-Pabón, W. & Klingelhutz, A. J. (2015). Does Staphylococcus aureus have a role in the development of Type 2 diabetes mellitus?. Future Microbiol, 10(10), 1549-52. PMID: 26439811.

Assimacopolous, A. P., Salgado-Pabón, W. & Schlievert, P. M. (2015). Staphylococcal and streptococcal toxic shock and Kawasaki syndromes. In D. Schlossberg (Eds.) Clinical Infectious Diseases. (2nd), pp. 127-132. Cambridge University Press.

Vu, B. G., Stach, C. S., Salgado-Pabón, W., Diekema, D. J., Gardner, S. E. & Schlievert, P. M. (2014). Superantigens of Staphylococcus aureus from patients with diabetic foot ulcers. J Infect Dis, 210(12), 1920-7. PMID: 24951827.

Pachulec, E., Siewering, K., Bender, T., Heller, E. M., Salgado-Pabón, W., Schmoller, S. K., Woodhams, K. L., Dillard, J. P. & van der Does, C. (2014). Functional analysis of the Gonococcal Genetic Island of Neisseria gonorrhoeae. PLoS One, 9(10), e109613. PMID: 25340397.

Salgado-Pabón, W., Herrera, A., Vu, B. G., Stach, C. S., Merriman, J. A., Spaulding, A. R. & Schlievert, P. M. (2014). Staphylococcus aureus ß-toxin production is common in strains with the ß-toxin gene inactivated by bacteriophage. J Infect Dis, 210(5), 784-92. PMID: 24620023.

Salgado-Pabón, W., Schlievert, P. M. (2014). Models matter: the search for an effective Staphylococcus aureus vaccine. Nat Rev Microbiol, 12(8), 585-91. PMID: 24998740.

Kulhankova, K., King, J. M. & Salgado-Pabón, W. (2014). Staphylococcal toxic shock syndrome: superantigen-mediated enhancement of endotoxin shock and adaptive immune suppression. Immunol Res, 59(1-3), 182-7. PMID: 24816557.

Spaulding, A. R., Salgado-Pabón, W., Merriman, J. A., Stach, C. S., Ji, Y., Gillman, A. N., Peterson, M. L. & Schlievert, P. M. (2014). Vaccination against Staphylococcus aureus pneumonia. J Infect Dis, 209(12), 1955-62. PMID: 24357631.

Salgado-Pabón, W., Konradt, C., Sansonetti, P. J. & Phalipon, A. (2014). New insights into the crosstalk between Shigella and T lymphocytes. Trends Microbiol, 22(4), 192-8. PMID: 24613405.

Salgado-Pabón, W., Case-Cook, L. C. & Schlievert, P. M. (2014). Molecular analysis of staphylococcal superantigens. pp. 169-85. Methods Mol Biol. PMID: 24085696.

Schlievert, P. M., Merriman, J. A., Salgado-Pabón, W., Mueller, E. A., Spaulding, A. R., Vu, B. G., Chuang-Smith, O. N., Kohler, P. L. & Kirby, J. R. (2013). Menaquinone analogs inhibit growth of bacterial pathogens. Antimicrob Agents Chemother, 57(11), 5432-7. PMID: 23959313.

Salgado-Pabón, W., Breshears, L., Spaulding, A. R., Merriman, J. A., Stach, C. S., Horswill, A. R., Peterson, M. L. & Schlievert, P. M. (2013). Superantigens are critical for Staphylococcus aureus Infective endocarditis, sepsis, and acute kidney injury. MBio, 4(4), e00494-13. PMID: 23963178.

Spaulding, A. R., Salgado-Pabón, W., Kohler, P. L., Horswill, A. R., Leung, D. Y. & Schlievert, P. M. (2013). Staphylococcal and streptococcal superantigen exotoxins. Clin Microbiol Rev, 26(3), 422-47. PMID: 23824366.

Brosnahan, A. J., Merriman, J. A., Salgado-Pabón, W., Ford, B. & Schlievert, P. M. (2013). Enterococcus faecalis inhibits superantigen toxic shock syndrome toxin-1-induced interleukin-8 from human vaginal epithelial cells through tetramic acids. PLoS One, 8(4), e61255. PMID: 23613823.

Salgado-Pabón, W., Celli, S., Arena, E. T., Nothelfer, K., Roux, P., Sellge, G., Frigimelica, E., Bousso, P., Sansonetti, P. J. & Phalipon, A. (2013). Shigella impairs T lymphocyte dynamics in vivo. Proc Natl Acad Sci USA, 110(12), 4458-63. PMID: 23417297.

Walker, J. N., Crosby, H. A., Spaulding, A. R., Salgado-Pabón, W., Malone, C. L., Rosenthal, C. B., Schlievert, P. M., Boyd, J. M. & Horswill, A. R. (2013). The Staphylococcus aureus ArlRS two-component system is a novel regulator of agglutination and pathogenesis. PLoS Pathog, 9(12), e1003819. PMID: 24367264.

Konradt, C., Frigimelica, E., Nothelfer, K., Puhar, A., Salgado-Pabón, W., di Bartolo, V., Scott-Algara, D., Rodrigues, C. D., Sansonetti, P. J. & Phalipon, A. (2011). The Shigella flexneri type three secretion system effector IpgD inhibits T cell migration by manipulating host phosphoinositide metabolism. Cell Host Microbe, 9(4), 263-72. PMID: 21501826.

Salgado-Pabón, W., Du, Y., Hackett, K. T., Lyons, K. M., Arvidson, C. G. & Dillard, J. P. (2010). Increased expression of the type IV secretion system in piliated Neisseria gonorrhoeae variants. J Bacteriol, 192(7), 1912-20. PMID: 20139191.

Sellge, G., Magalhaes, J. G., Konradt, C., Fritz, J. H., Salgado-Pabón, W., Eberl, G., Bandeira, A., Di Santo, J. P., Sansonetti, P. J. & Phalipon, A. (2010). Th17 cells are the dominant T cell subtype primed by Shigella flexneri mediating protective immunity. J Immunol, 184(4), 2076-85. PMID: 20089698.

Salgado-Pabón, W., Jain, S., Turner, N., van der Does, C. & Dillard, J. P. (2007). A novel relaxase homologue is involved in chromosomal DNA processing for type IV secretion in Neisseria gonorrhoeae. Mol Microbiol, 66(4), 930-47. PMID: 17927698.