S. CHATELLIER*, F. KHAMBATY, H. BASMA, Y. GUEDEZ, A. NORRBY-TEGLUND, L. TRPESKY, D.E. LOW, A. MCGEER, and M. KOTB, VA Med. Ctr., Memphis, TN, U.S. FDA, Washington, DC, Mount Sinai Hosp., Toronto, Canada, Univ. of TN, Memphis, TN.

Recent studies have suggested that host immunogenetic factors play a major role in determining the outcome of invasive group A streptococcal (GAS) infections. In an effort to directly investigate this issue, we identified a cohort of 35 patients from Ontario, Canada, who were infected with M1T1 strains and could be clinically classified as severe (n=22) and nonsevere (n=13) invasive GAS infection cases. The relatedness of these strains was investigated by a variety of molecular methods. Sequencing of the M1 gene from 19 representative isolates (10 emm1.0 allele. PCR typing of streptococcal pyrogenic exotoxin (spe) superantigen genes indicated the presence of speA, speB, and speF in all isolates. Sequencing of the speA gene in 17 representative isolates from severe cases revealed that all isolates tested harbored the apeA2 allele. Further molecular genotyping was done on 25 isolates (15 from severe and 10 from nonsevere cases) by Random Amplified Polymorphic DNA analysis (RAPD) and Pulsed-Field Gel Electrophoresis (PFGE). All strains except one exhibited a unique RAPD type by using 2 primers. PFGE was more discriminative than RAPD, revealing that 21 out of 25 strains were identical after digestion with SmaI. The 4 divergent strains (2 from severe and 2 from nonsevere cases) were assigned to 3 patterns all lacking one band and having at least one-extra-band. The 21 strains sharing the same PFGE pattern with SmaI were also tested with SfiI. A unique pattern was identified for 20 strains. The divergent strain exhibited a pattern with a missing band and two additional bands. The phenotypic expression of superantigens SpeA, SpeB, and SpeF proteins varied among the M1T1 isolates, but there was no correlation between the amount expressed and disease severity. In conclusion, the majority of M1T1 isolates were genotypically indistinguishable and were similarly distributed among the severe and non-severe cases. This study adds to the growing evidence that immunogenetic host factors of patients infected with genotypically similar strains may modulate the severity of invasive GAS disease.

Presented at:

38^th INTERSCIENCE CONFERENCE ON ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (ICAAC), San Diego, CA , Sept 26-29, 1998. Session 177-G, Paper G-101.