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Infection and Immunity, January 2000, p. 133-140, Vol. 68, No. 1
Molecular Microbiology Unit, Women's and
Children's Hospital, North Adelaide, South Australia 5006, Australia
Received 2 June 1999/Returned for modification 5 August
1999/Accepted 26 October 1999
Although the polysaccharide capsule of Streptococcus
pneumoniae has been recognized as a sine qua non of virulence,
much recent attention has focused on the role of pneumococcal proteins
in pathogenesis, particularly in view of their potential as vaccine antigens. The individual contributions of pneumolysin (Ply), the major
neuraminidase (NanA), autolysin (LytA), hyaluronidase (Hyl), pneumococcal surface protein A (PspA), and choline-binding protein A
(CbpA) have been examined by specifically mutagenizing the respective genes in the pneumococcal chromosome and comparing the impact on
virulence in a mouse intraperitoneal challenge model. Mutagenesis of
either the ply, lytA, or pspA gene
in S. pneumoniae D39 significantly reduced virulence,
relative to that of the wild-type strain, indicating that the
respective gene products contribute to pathogenesis. On the other hand,
mutations in nanA, hyl, or cbpA had
no significant impact. The virulence of D39 derivatives carrying a
ply deletion mutation as well as an insertion-duplication
mutation in one of the other genes was also examined. Mutagenesis of
either nanA or lytA did not result in an
additional attenuation of virulence in the ply deletion
background. However, significant additive attenuation in virulence was
observed for the strains with ply-hyl, ply-pspA, and ply-cbpA double mutations.
0019-9567/0/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Additive Attenuation of Virulence of
Streptococcus pneumoniae by Mutation of the Genes Encoding
Pneumolysin and Other Putative Pneumococcal Virulence
Proteins
*
Corresponding author. Mailing address: Molecular
Microbiology Unit, Women's and Children's Hospital, North Adelaide,
S.A. 5006, Australia. Phone: 61-8-8204 6302. Fax: 61-8-8204 6051. E-mail: patonj{at}wch.sa.gov.au.
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