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Changes in virulence, M protein and IgG Fc receptor activity in a type 12 group A streptococcal strain during mouse
Abstract:
A type 12 group A strain (1800) was passaged serially through mice 25 times. The ability to servive in normal human blood dropped from a growth index of 52 after the first passage to 1 after four passages. After 14 passages the growth index increased again and stabilized above 30. The virulence for mice increased from a LD100 of 10(8) colony forming units (CFU) to 10-100 CFU after 7 passages and then remained constant. The Mqw antigen disappeared after 4 passages as tested by immunodiffusion, electroimmunoassay and indirect bactericidal tests. Three antisera, raised in rabbits against strains originally belonging to types M3, M12 and M46 but devoid of type antigens after mouse passages showed high bactericidal indices against the 1800 strain after 14 or more passages on mice. Anti-type M1 serum was also found bactericidal for the passaged strains. The IgG Fc-receptor activity of the strain isolated after each mouse passage was tested in hemagglutination experiments with human red blood cells coated with "incomplete" anti-Rh and hot hydrochloric acid extracts of the strains. The capacity to agglutinate "Ripley"-coated cells increased gradually during the first 12 passages and subsequently the titres of the extracts stabilized between 1:160 and 1:320. The HUN coat, useful for detection of the G3m (5) maraker gave titraes increasing with the number of passages while the titres for IgG1 coats kept at 1:4 or below. On background of these results, the possible role of the IgG Fc-receptor as a virulence factor is discussed.
Insights
Serial mouse passages altered group A Streptococcus virulence and immune evasion. The IgG Fc-receptor emerged as a potential virulence factor, influencing bacterial survival and host immune response.
Area of Science:
- Microbiology
- Immunology
- Bacterial Pathogenesis
Background:
- Group A Streptococcus (GAS) virulence factors are crucial for pathogenesis.
- Understanding GAS adaptation during host passage is key to identifying virulence mechanisms.
Purpose of the Study:
- To investigate the impact of serial mouse passages on GAS strain 1800.
- To characterize changes in bacterial virulence, immune evasion, and Fc-receptor activity.
Main Methods:
- Serial passage of GAS strain 1800 in mice.
- Assessment of bacterial survival in human blood (growth index).
- Determination of mouse LD100 (lethal dose for 50% of subjects).
- Immunodiffusion, electroimmunoassay, and indirect bactericidal tests for antigen analysis.
- Hemagglutination assays to evaluate IgG Fc-receptor activity.
Main Results:
- Bacterial survival in human blood initially decreased then increased after 14 passages.
- Mouse virulence significantly increased after 7 passages.
- The Mqw antigen disappeared, while IgG Fc-receptor activity and specific antibody responses changed.
- Increased IgG Fc-receptor activity correlated with passages and specific antibody interactions.
Conclusions:
- Serial mouse passage induces significant adaptive changes in GAS.
- The IgG Fc-receptor may play a role as a virulence factor in GAS pathogenesis.
- These findings offer insights into bacterial adaptation and immune evasion strategies.