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Infection and Immunity, December 2008, p. 5738-5744, Vol. 76, No. 12
0019-9567/08/$08.00+0     doi:10.1128/IAI.00874-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Antibodies to Capsular Polysaccharide and Clumping Factor A Prevent Mastitis and the Emergence of Unencapsulated and Small-Colony Variants of Staphylococcus aureus in Mice{triangledown}

Lorena P. N. Tuchscherr,1 Fernanda R. Buzzola,1,2 Lucía P. Alvarez,1,2 Jean C. Lee,3 and Daniel O. Sordelli1,2*

Department of Microbiology, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina,1 CONICET, Buenos Aires, Argentina,2 Channing Laboratory, Department of Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts3

Received 15 July 2008/ Returned for modification 27 August 2008/ Accepted 17 September 2008

The pathogenesis of Staphylococcus aureus infections is influenced by multiple virulence factors that are expressed under variable conditions, and this has complicated the design of an effective vaccine. Clinical trials that targeted the capsule or clumping factor A (ClfA) failed to protect the recipients against staphylococcal infections. We passively immunized lactating mice with rabbit antibodies to S. aureus capsular polysaccharide (CP) serotype 5 (CP5) or CP8 or with monoclonal antibodies to ClfA. Mice immunized with antibodies to CP5 or CP8 or with ClfA had significantly reduced tissue bacterial burdens 4 days after intramammary challenge with encapsulated S. aureus strains. After several passages in mice passively immunized with CP-specific antiserum, increasing numbers of stable unencapsulated variants of S. aureus were cultured from the infected mammary glands. Greater numbers of these unencapsulated S. aureus variants than of the corresponding encapsulated parental strains were internalized in vitro in MAC-T bovine cells. Furthermore, small-colony variants (SCVs) were recovered from the infected mammary glands after several passages in mice passively immunized with CP-specific antiserum. A combination of antibodies effectively sterilized mammary glands in a significant number of passively immunized mice. More importantly, passive immunization with antibodies to both CP and ClfA fully inhibited the emergence of unencapsulated "escape mutants" and significantly reduced the appearance of SCVs. A vaccine formulation comprising CP conjugates plus a surface-associated protein adhesin may be more effective than either antigen alone for prevention of S. aureus infections.

* Corresponding author. Mailing address: Department of Microbiology, School of Medicine, University of Buenos Aires, Paraguay 2155 P-12, C1121ABG Buenos Aires, Argentina. Phone: 5411 5950 9618. Fax: 5411 4964 2554. E-mail: sordelli{at}fmed.uba.ar

{triangledown} Published ahead of print on 22 September 2008.

Editor: V. J. DiRita

Infection and Immunity, December 2008, p. 5738-5744, Vol. 76, No. 12
0019-9567/08/$08.00+0     doi:10.1128/IAI.00874-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Glowalla, E., Tosetti, B., Kronke, M., Krut, O. (2009). Proteomics-Based Identification of Anchorless Cell Wall Proteins as Vaccine Candidates against Staphylococcus aureus. Infect. Immun. 77: 2719-2729 [Abstract] [Full Text]  
  • Lattar, S. M., Tuchscherr, L. P. N., Caccuri, R. L., Centron, D., Becker, K., Alonso, C. A., Barberis, C., Miranda, G., Buzzola, F. R., von Eiff, C., Sordelli, D. O. (2009). Capsule Expression and Genotypic Differences among Staphylococcus aureus Isolates from Patients with Chronic or Acute Osteomyelitis. Infect. Immun. 77: 1968-1975 [Abstract] [Full Text]  


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