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. 2001 Jul 31;98(16):9365-70.
doi: 10.1073/pnas.161175598. Epub 2001 Jul 24.

Structural rationale for the modulation of abscess formation by Staphylococcus aureus capsular polysaccharides

A O Tzianabos  1 , J Y Wang, J C Lee
Affiliations

Structural rationale for the modulation of abscess formation by Staphylococcus aureus capsular polysaccharides

A O Tzianabos et al. Proc Natl Acad Sci U S A. .

Abstract

Staphylococcus aureus is a medically important bacterial pathogen that is a common cause of superficial and deep-seated abscesses in humans. Most S. aureus isolates produce either a serotype 5 or 8 capsular polysaccharide (CP) that has been shown to enhance bacterial virulence. We investigated the role of S. aureus CPs in modulating abscess formation in an experimental animal model of intraabdominal infection. Structural studies of CP8 revealed that it has a zwitterionic charge motif conferred by the negatively charged carboxyl group of N-acetylmannosaminuronic acid and free amino groups available on partially N-acetylated fucosamine residues. We report that purified CP5 and CP8 facilitated intraabdominal abscess formation in animals when given i.p. with a sterile cecal contents adjuvant. Chemical modifications that neutralized the positively or negatively charged groups on CP8 abrogated its ability to provoke abscesses. Rats prophylactically treated with CP8 s.c. were protected against abscess formation induced by homologous or heterologous zwitterionic polysaccharides. Likewise, treatment with CP8 protected against challenge with viable S. aureus strains PS80 (a capsule type 8 strain) or COL (a methicillin-resistant capsule type 5 strain). Purified CP8 was a potent activator of rat and human CD4(+) T cells in vitro. When transferred to naive rats, these activated T cells modulated the development of intraabdominal abscess formation. These results provide a structure/function rationale for abscess formation by S. aureus and expand the sphere of encapsulated organisms that interact directly with T cells to regulate this host response to bacterial infection.

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Figures

Figure 1
Figure 1
Abscess induction by S. aureus. (A) Rats were challenged with live or formalin-killed S. aureus Reynolds cells. (B) Dose titration curves for serotype 5 strain Reynolds, the acapsular mutant JL243, and serotype 8 strain PS80. The calculated AD50 values for three strains were 60, 1.2 × 103, and 51 cfu, respectively.
Figure 2
Figure 2
Partial 1H NMR spectra of native and O-deacetylated CP8 showing the NAc and OAc methyl protons. (A) Native CP8 from Becker; (B) O-deacetylated Becker CP8; (C) native CP8 from strain O13; (D) O-deacetylated CP8 from strain O13. The spectra in B and D indicate that CP8 from strains Becker and O13 have different degree of N-acetylation. CP8 from strains O13 and PS80 have nearly identical NMR spectra.
Figure 3
Figure 3
Purified CP8 elicited a potent proliferative response in both human (A) and rat (B) T cells. Activation of human T cells by S. pneumoniae CP1 and S. aureus CP8 peaked at day 9 postculture (A), whereas the rat T cell response peaked on day 6 (B).
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