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The hemolytic and complement-activating properties of pneumolysin do not contribute individually to virulence in a
K A Benton1, J C Paton, D E Briles
1Department of Microbiology, The University of Alabama at Birmingham, Birmingham, AL 35294-2170, USA.
Abstract:
The virulence of pneumococcal capsular type 2 strain D39 and derivatives with mutations in the pneumolysin gene were examined in a mouse bacteremia model. In CBA/N-XID mice D39 is known to exhibit exponential growth in the blood until the death of the mice at 24 to 36 h. In contrast, PLN, a pneumolysin-deficient derivative of D39, reaches a plateau in growth that is maintained for several days. The growth patterns of D39 and PLN observed in CBA/N-XID mice were also observed in C3H/HeJ and C3H/HeOuJ mice, but not in 129/SvJ and C57BL/6J mice. These results demonstrate that the effect of pneumolysin on bacteremia is dependent on the genetic background of the mice. D39 derivatives with point mutations which abolish the cytotoxic or complement-activating properties of pneumolysin did not have major individual effects on virulence in CBA/N- XID and C3H/HeOuJ mice. A derivative with mutations affecting both the cytotoxic and complement- activating properties resulted in a modest, yet statistically significant, increase in survival time of i.v. challenged CBA/N-XID mice. However, the effect was less marked than that seen with PLN. These findings suggest that the virulence effects of pneumolysin in bacteremia must be due in part to properties other than hemolysis and complement fixation.
Insights
Pneumolysin
Area of Science:
- Microbiology
- Immunology
- Genetics
Background:
- Streptococcus pneumoniae causes invasive pneumococcal disease.
- Pneumolysin is a key virulence factor of S. pneumoniae.
- The role of pneumolysin in bacteremia is not fully understood.
Purpose of the Study:
- To investigate the role of pneumolysin in pneumococcal bacteremia.
- To determine the influence of mouse genetic background on pneumolysin's virulence.
- To elucidate the specific properties of pneumolysin contributing to virulence.
Main Methods:
- Mouse bacteremia model using Streptococcus pneumoniae strain D39 and its derivatives.
- Comparison of bacterial growth and survival in different mouse strains (CBA/N-XID, C3H/HeJ, C3H/HeOuJ, 129/SvJ, C57BL/6J).
- Analysis of pneumolysin derivatives with mutations affecting cytotoxicity and complement activation.
Main Results:
- Pneumolysin deficiency (PLN) significantly altered bacterial growth patterns in susceptible mouse strains.
- The impact of pneumolysin on bacteremia is dependent on the host's genetic background.
- Mutations affecting pneumolysin's cytotoxic and complement-activating functions had limited individual effects on virulence.
Conclusions:
- Pneumolysin contributes to pneumococcal virulence in a genetically dependent manner.
- Properties of pneumolysin beyond hemolysis and complement fixation are crucial for its role in bacteremia.
- Further research is needed to identify other virulence-associated functions of pneumolysin.