Pneumococcal surface protein A contributes to secondary Streptococcus pneumoniae infection after influenza virus
Quinton O King1, Benfang Lei, Allen G Harmsen
1Veterinary Molecular Biology, Montana State University, Bozeman, MT 59717-3610, USA. quinton_king@hotmail.com
Abstract:
We compared the growth of Streptococcus pneumoniae mutants with a disruption in the gene for either pneumococcal surface protein A (PspA-), neuraminidase A (NanA-), or hyaluronidase (Hyl-) to that of the parental strain D39 by means of a competitive growth model in mice with and those without prior influenza virus infection. The numbers of total bacteria recovered from mice with prior influenza virus infection were significantly greater than those recovered from mice without prior influenza virus infection. Although the Hyl- and NanA- mutants did not display attenuation in mice with or without prior influenza virus infection, the PspA- mutant exhibited attenuation both in mice with and in mice without prior influenza virus infection. This defect was severe in influenza virus-infected mice, for which growth of the PspA- mutant was 1800-fold lower than that of the parental strain D39. Furthermore, PspA immunization significantly reduced secondary bacterial lung burdens and concentrations of specific markers of lung damage in mice receiving serotypes 2, 3, and 4 pneumococci. Our findings indicate that PspA contributes to secondary S. pneumoniae infection after influenza virus infection and that PspA immunization mitigates early secondary pneumococcal lung infections.
Insights
Pneumococcal surface protein A (PspA) is crucial for Streptococcus pneumoniae growth after influenza infection in mice. PspA deficiency severely limits bacterial growth, and PspA immunization protects against secondary lung infections.
Area of Science:
- Microbiology
- Immunology
- Infectious Diseases
Background:
- Influenza virus infection predisposes individuals to secondary bacterial pneumonia.
- Streptococcus pneumoniae is a common cause of secondary bacterial pneumonia.
- Pneumococcal surface protein A (PspA) is a major virulence factor of S. pneumoniae.
Purpose of the Study:
- To investigate the role of PspA, NanA, and Hyl in S. pneumoniae pathogenesis following influenza virus infection.
- To evaluate the efficacy of PspA immunization in preventing secondary pneumococcal infections.
Main Methods:
- Competitive growth model in mice with and without prior influenza virus infection.
- Comparison of wild-type D39 strain with PspA-, NanA-, and Hyl- mutants.
- Assessment of bacterial burden and lung damage markers post-infection.
- Evaluation of PspA immunization efficacy.
Main Results:
- Influenza virus infection significantly increased S. pneumoniae recovery.
- PspA- mutant showed severe attenuation in both non-infected and influenza-infected mice, with 1800-fold lower growth in the latter.
- NanA- and Hyl- mutants did not exhibit significant attenuation.
- PspA immunization reduced bacterial lung burden and lung damage markers.
Conclusions:
- PspA is essential for S. pneumoniae virulence, particularly during secondary infections following influenza.
- PspA contributes significantly to S. pneumoniae pathogenesis after viral respiratory infections.
- PspA-based immunization is a promising strategy to prevent secondary pneumococcal lung infections.
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