Characterization of a Mouse-Passaged, Highly Encapsulated Variant of Group A Streptococcus in In Vitro and In Vivo Studies

• Published in: The Journal of infectious diseases 2000-12, Vol.182 (6), p.1702-1711
• Main Authors: Ravins, Miriam, Jaffe, Joseph, Hanski, Emanuel, Shetzigovski, Ilanit, Natanson-Yaron, Shira, Moses, Allon E.
• Format: Article
• Language: English
• Subjects: Animals; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Bacteria; Bacterial Adhesion; Bacterial Capsules - genetics; Bacterial Proteins - analysis; Biological and medical sciences; Carrier Proteins; CsrRS protein; Encapsulation; Epithelial cells; Epithelial Cells - microbiology; Genes, Bacterial; Human viral diseases; Humans; Hyaluronic Acid - analysis; Infections; Infectious diseases; Lesions; Major Articles; Medical sciences; Membrane Proteins - analysis; Mice; Necrosis; Operon; Pharmacology. Drug treatments; Phenotype; Regulon; RNA; RNA, Bacterial - analysis; RNA, Messenger - genetics; Skin Diseases, Infectious - microbiology; Skin Diseases, Infectious - pathology; Soft Tissue Infections - microbiology; Soft Tissue Infections - pathology; Steepest descent method; Streptococcal Infections - microbiology; Streptococcal Infections - pathology; Streptococcus; Streptococcus pyogenes; Streptococcus pyogenes - genetics; Streptococcus pyogenes - pathogenicity; Streptolysins - analysis; Tumor Cells, Cultured; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Virulence; Virulence - genetics
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/317635

JRS4(HE), a highly encapsulated, mouse-passaged variant of group A streptococcal strain JRS4, was characterized. The mucoid phenotype of JRS4(HE) was preserved after extensive passage in vitro. The level and size of csrRS transcript in JRS4(HE) was similar to that of JRS4, yet JRS4(HE) expressed high levels of has and sagA and exhibited an increased activity of streptolysin S. These findings indicate that the CsrRS repressor system was inactive in JRS4(HE). JRS4(HE) adhered to HEp-2 cells at the stationary phase but did not internalize these cells. At midlogarithmic phase, JRS4(HE) neither adhered to nor internalized cells, because of an increased amount of hyaluronic acid. Mice injected subcutaneously with JRS4(HE) developed large, deep necrotic lesions. In contrast, mice challenged with JRS4 developed small, superficial lesions. Despite the use of a high inoculum, mice challenged with JRS4(HE) did not develop a lethal bacteremic infection. It is concluded that inactivation of CsrRS in vivo is insufficient to cause a spreading necrotic disease.