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Antigenic and Biological Characteristics of Mutant Strains of Cryptococcus neoformans Lacking Capsular O Acetylation or Xylosyl Side Chains

Department of Microbiology and Immunology, University of Nevada School of Medicine, Reno, Nevada 89557,¹ Evans Memorial Department of Clinical Research and Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118,² Unité de Mycologie Moléculaire, Institut Pasteur, 75724 Paris Cedex, France³

Received 20 December 2002/ Returned for modification 24 January 2003/ Accepted 18 February 2003

Cryptococcus neoformans is surrounded by an antiphagocytic polysaccharide capsule whose primary constituent is glucuronoxylomannan (GXM). Three prominent structural features of GXM are single xylosyl and glucuronosyl side chains and O acetylation of the mannose backbone. Isogenic pairs of O-acetyl-positive and O-acetyl-negative strains (cas1) as well as xylose-positive and xylose-negative strains (uxs1) of serotype D have been reported. The cas1 strains were hypervirulent, and the uxs1 strains were avirulent. The goal of this study was to examine the effects of the cas1 and uxs1 mutations on the following: (i) binding of anti-GXM monoclonal antibodies (MAbs) in capsular quellung reactions, (ii) activation of the complement system and binding of C3, (iii) phagocytosis by neutrophils, and (iv) clearance of GXM in vivo. The results showed that loss of O acetylation produced dramatic changes in the reactivities of five of seven anti-GXM MAbs. In contrast, loss of xylosylation produced a substantive alteration in the binding behavior of only one MAb. O-acetyl-negative strains showed no alteration in activation and binding of C3 from normal serum. Xylose-negative strains exhibited accelerated kinetics for C3 deposition. Loss of O acetylation or xylosylation had no effect on phagocytosis of serum-opsonized yeast cells by human neutrophils. Finally, loss of O acetylation or xylosylation altered the kinetics for clearance of GXM from serum and accumulation of GXM in the liver and spleen. These results show that O acetylation and/or xylosylation are important for binding of anti-GXM MAbs, for complement activation, and for tissue accumulation of GXM but do not impact phagocytosis by neutrophils.

Editor: J. T. Barbieri

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