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Infection and Immunity, March 2000, p. 1215-1221, Vol. 68, No. 3
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Role of Group A Streptococcal Virulence Factors in Adherence to Keratinocytes

Gary L. Darmstadt,1,2 Laurel Mentele,1 Andreas Podbielski,3 and Craig E. Rubens1,*

Departments of Pediatrics1 and Medicine,2 University of Washington School of Medicine, Seattle, Washington 98105, and Department of Medical Microbiology and Hygiene, University Hospital Ulm, Ulm, Germany3

Received 5 October 1999/Returned for modification 2 November 1999/Accepted 24 November 1999

To evaluate the role of putative group A streptococcal virulence factors in the initiation of skin infections, we compared the adherence of a wild-type M49-protein skin-associated strain to that of a series of 16 isogenic mutants created by insertional inactivation of virulence genes. None of the mutants, including the M-protein-deficient (emm mutant) strain, displayed reduced adherence to early-passage cultured human keratinocytes, but adherence of the mutant lacking hyaluronic acid capsule expression (has mutant) was increased 13-fold. In contrast, elimination of capsule expression in M2-, M3-, and M18-protein has mutants increased adherence only slightly (1.3- to 2.3-fold) compared to their respective wild-type strains. A mutant with inactivation of both emm and has displayed high-level adherence (34.9 ± 4.1%) equal to that of the has mutant strain (40.7 + 8.0%), confirming the lack of involvement of M49 protein in attachment. Moreover, adherence of the M49-protein-deficient (emm mutant) and wild-type strains was increased to the same level (57 and 55%, respectively) following enzymatic digestion of their hyaluronic acid capsule. Adherence of mutants lacking oligopeptide permease (Opp) expression was increased 3.8- to 5.5-fold, in association with decreased cell-associated hyaluronic acid capsule. Finally, soluble CD46 failed to inhibit adherence of M49- and M52-serotype skin strains. We conclude that (i) bacterial M protein and keratinocyte CD46 do not mediate adherence of M49 skin-associated Streptococcus pyogenes to epidermal keratinocytes, (ii) hyaluronic acid capsule impedes the interaction of bacterial adhesins with keratinocyte receptors, (iii) modulation of capsule expression may be important in the pathogenesis of skin infections, and (iv) the molecular interactions in attachment of skin strains of S. pyogenes to keratinocytes are unique and remain unidentified.

* Corresponding author. Mailing address: Division of Infectious Diseases, Children's Hospital & Regional Medical Center, 4800 Sand Point Way NE, CH-32, Seattle, WA 98105. Phone: (206) 526-2073. Fax: (206) 527-3890. E-mail: cruben{at}chmc.org.

Infection and Immunity, March 2000, p. 1215-1221, Vol. 68, No. 3
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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