Molecular mechanisms of blister formation in bullous impetigo and staphylococcal scalded skin syndrome

Yasushi Hanakawa, Norman M. Schechter, Chenyan Lin, Luis Garza, Hong Li, Takayuki Yamaguchi, Yasuyuki Fudaba, Koji Nishifuji, Motoyuki Sugai, Masayuki Amagai, John R. Stanley

Research output: Contribution to journalArticle

147 Citations (Scopus)

Abstract

Bullous impetigo due to Staphylococcus aureus is one of the most common bacterial infections of man, and its generalized form, staphylococcal scalded skin syndrome (SSSS), is a frequent manifestation of staphylococcal epidemics in neonatal nurseries. Both diseases are mediated by exfoliative toxins (ETs), which show exquisite pathologic specificity in blistering only the superficial epidermis. We show that these toxins act as serine proteases with extremely focused molecular specificity to cleave mouse and human desmoglein 1 (Dsg1) once after glutamic acid residue 381 between extracellular domains 3 and 4. Mutation of the predicted catalytically active serine to alanine completely inhibits cleavage. The mutated ETs bind specifically to Dsg1 by immunofluorescence colocalization and by coimmunoprecipitation. Thus, ETs, through specific recognition and proteolytic cleavage of one structurally critical peptide bond in an adhesion molecule, cause its dysfunction and allow S. aureus to spread under the stratum corneum, the main barrier of the skin, explaining how, although they circulate through the entire body in SSSS, they cause pathology only in the superficial epidermis.

Original languageEnglish
Pages (from-to)53-60
Number of pages8
JournalJournal of Clinical Investigation
Volume110
Issue number1
DOIs
Publication statusPublished - 2002 Jan 1

    Fingerprint

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Hanakawa, Y., Schechter, N. M., Lin, C., Garza, L., Li, H., Yamaguchi, T., Fudaba, Y., Nishifuji, K., Sugai, M., Amagai, M., & Stanley, J. R. (2002). Molecular mechanisms of blister formation in bullous impetigo and staphylococcal scalded skin syndrome. Journal of Clinical Investigation, 110(1), 53-60. https://doi.org/10.1172/JCI0215766