Microbial Pathogenesis 1995; 19:299-315 Biological properties of a Streptococcus pyogenes mutant generated by Tn916 insertion in mga Britt-Marie Kihlberg, 1 Jakki Cooney, 1. Michael G. Caparon, z Arne OIs6n ~ and Lars Bj6rckH" 1Department of Cell and Molecular Biology, Section for Molecular Pathogenesis, Lund University, Box 94, S-221 O0 Lund, Sweden and 2Department of Molecular Microbiology, Washington University School of Medicine, Box 8230, St. Louis, Missouri 63110-1093, U.S.A (Received August 23, 1995; accepted August 25, 1995) Kihlberg, B.-M. (Department of Cell and Molecular Biology, Section for Molecular Patho- genesis, Lund University, Box 94, S-221 00 Lund, Sweden), J. Cooney, M. G. Caparon, A. Olsdn and L. BjSrck. Biological properties of a Streptococcus pyogenes mutant generated by Tn916 insertion in toga. Microbial Pathogenesis 1995; 19: 299-315. The toga regulon of Streptococcus pyogenes contains genes which contribute to the patho- genicity and virulence of this significant human pathogen, Transposon insertional inactivation of the regulatory toga gene in a S. pyogenes strain of the clinically important M1 serotype, blocked the expression of four genes located downstream of toga. These genes encode the M1 protein, the IgG-binding protein H, protein SIC which is an extracellular inhibitor of complement, and the C5a peptidase which interferes with granulocyte migration. The wild- type strain is resistant to phagocytosis and adheres to human skin tissue sections; properties that were lost in the transposon mutant. Moreover, the mutant was less virulent to mice but more cytolytic to human lymphocytes, the latter due to an increased activity of streptolysin S, whereas the production of streptolysin O, another toxin of S. pyogenes, was not affected. The toga mutation was complemented in trans with an intact mga gene which restored the phenotype of the wild-type strain. © 1995 Academic Press Limited Key words: streptococcus, mutant, gene, protein, hemolysin, virulence. Introduction Streptococcus pyogenes are important pathogenic bacteria in humans causing sup- purative infections like tonsillitis and erysipelas, whereas rheumatic fever and glo- merulonephritis are serious clinical sequelae following acute S. pyogenes infections. Apart from a number of extracellular toxins and enzymes 1'2 S. pyogenes expresses a group of cell surface-associated proteins 3 which also contribute to their patho- genicity and virulence. Among these surface proteins, M protein was the first to be isolated and characterized. 4 The protein exists in more than 80 different serotypes and is a virulence determinant due to its antiphagocytic property. M protein has * Present address: Department of Chemistry and Biochemistry, Massey University, Palmerston North, New Zealand. t Author to whom correspondence should be addressed: Lars Bj6rck, Departmentof Cell and Molecular Biology, Section for Molecular Pathogenesis,Lund University, P.O. Box 94, S-221 00 LUND, Sweden. 0882-4010/95/110299+17$12.00/0 © 1995Academic Press Limited