HUMAR D, DATTA V, BAST DJ, DE AZAVEDO JC, NIZET V; Interscience Conference on Antimicrobial Agents and Chemotherapy.

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2000 Sep 17-20; 40: 43.

Univ. of California, San Diego, La Jolla, CA

BACKGROUND: Rarely, Group G streptococci (GGS) produce severe invasive infections. We hypothesized that GGS production of such infections is in part due to the beta-hemolytic phenotype it shares with group A Streptococcus (GAS).METHODS: A beta-hemolytic GGS was isolated from a patient with necrotizing fasciitis (NF). In GAS, the beta-hemolysin streptolysin S (SLS) is encoded by the sag operon, including the putative structural gene sagA and downstream genes (sagB -I) thought to play roles in processing and export of the mature toxin. We used genetic analysis, targeted mutagenesis and a mouse model of NF to determine whether (1) SLS is also the beta-hemolysin of GGS and (2) the contribution of this toxin to GGS invasive disease.RESULTS: PCR analysis of chromosomal DNA from the GGS clinical isolate using specific GAS sag primers revealed homologues of all 9 genes. Direct sequencing of sagA from GGS showed 100% nucleotide identity with the GAS sagA gene. Plasmid integrational mutagenesis of sagA in GGS resulted in loss of the beta-hemolytic phenotype. SLS activity of this nonhemolytic (NH) GGS mutant could be restored by introduction of the GAS sag locus on a plasmid vector. When injected subcutaneously into mice, the GGS clinical isolate invariably elicited a necrotic ulcer, with bacterial proliferation, neutrophilic inflammation and histopathologic evidence of NF. In contrast, mice infected with the NH GGS mutant did not develop ulcers. Biopsy of the inoculation site demonstrated bacterial clearance (P < 0.01) and minimal degrees of inflammation or tissue injury. Conclusion: The beta-hemolysin of GGS is in fact SLS, encoded by the same 9-gene operon (sag) possessed by GAS. SLS expression contributes to the pathogenesis of invasive GGS infections.KEYWORDS: Group G streptococcus; Necrotizing fasciitis; Streptolysin S

Publication Types:

• Meeting Abstracts

Keywords:

• Animals
• Bacterial Proteins
• Fasciitis, Necrotizing
• Hemolysin Proteins
• Humans
• Mice
• Operon
• Soft Tissue Infections
• Streptococcal Infections
• Streptococcus
• Streptolysins
• genetics
• streptolysin S

Other ID:

• GWAIDS0009764

UI: 102247262

From Meeting Abstracts