Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2011 Oct;21(5):597-602.
doi: 10.1016/j.sbi.2011.08.006. Epub 2011 Sep 1.

Emerging themes in cryptococcal capsule synthesis

Pardeep Kumar  1 , Meng Yang, Brian C Haynes, Michael L Skowyra, Tamara L Doering
Affiliations
Review

Emerging themes in cryptococcal capsule synthesis

Pardeep Kumar et al. Curr Opin Struct Biol. 2011 Oct.

Abstract

Cryptococcus neoformans, a basidiomycete yeast and opportunistic pathogen, expends significant biosynthetic effort on construction of a polysaccharide capsule with a radius that may be many times that of the cell. Beyond posing a stimulating challenge in terms of defining biosynthetic pathways, the capsule is required for this yeast to cause fatal disease. This combination has focused the attention of researchers on this system. Here we briefly review two aspects of the rapidly advancing field of capsule synthesis: the extensive variation that occurs in capsule polymers and the regulation of capsule biosynthesis.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Cryptococcal surface structures. This quick-freeze deep-etch electron micrograph of the edge of a cryptococcal cell (J. Heuser and T.L. Doering, unpublished) shows a segment of the cell wall separating a region of the plasma membrane from the radiating capsule fibers. The capsule extends upwards from the cell body and only the inner portion of the structure is visible; the entire capsule would extend significantly beyond the region shown.
Figure 2
Figure 2
Schematic depiction of the cryptococcal capsule polysaccharides. Single polymer repeat units are shown and all sugars are in the pyranose form unless labeled with f to indicate furanose. Top, the six structural reporter groups that are found in varying proportions in glucuronoxylomannan (GXM) from different strains of C. neoformans (as defined by Cherniak et al [14]). All linkages are as indicated on the M4 structure. Mannose residues, green spheres; xylose, red stars; glucuronic acid residues, half filled diamonds. Mannose acetylation is not shown. Bottom, the structure of glucuronoxylomannogalactan (GXMGal). Trisaccharide side branches that occur at every other galactose may be substituted on 0 – 3 moieties [16,17]; the two extreme cases are shown. Symbols are as above, with galactose shown as yellow spheres. Some unbranched backbone galactose residues are modified with β-1,2 and β-1,3-linked galactofuranose as shown (C. Heiss, M. Skowyra, and T. Doering, unpublished data). Shapes and colors follow the recommendations of the Consortium for Functional Glycomics. This figure is modified from [9] according to the generous policy of Annual Reviews.
Figure 3
Figure 3
Growth conditions dramatically alter capsule thickness. Striking capsule induction is demonstrated by light micrographs of cells grown in an atmosphere of either room air (left) or 5% CO2 (right). Both cultures were grown for 24 hours at 37 °C in tissue culture medium and then stained with India ink; the capsule appears as a region of ink exclusion surrounding the cell. Scale bars, 10 microns.
Figure 4
Figure 4
Capsule is regulated by a complex network, as exemplified by this subset of regulatory interactions involving transcription factors that influence capsule size (red ovals; see text). Several of the interactions shown are mediated by Hog1, a MAP kinase involved in stress response and virulence factor synthesis in C. neoformans, which is phosphorylated by the MAPK kinase Pbs2 [39]. SAGA is a multiprotein complex that regulates transcription [48]; deletion of genes encoding two of its component proteins, Gcn5 and Ada2, yields hypocapsular cryptococci ([45] and our unpublished work, respectively). The diagram is based on our analysis of gene expression profiles generated by microarray [–43,46] or RNA sequencing (our unpublished data on strains deleted for NRG1, CIR1, and ADA2). Green lines, stimulation of transcription; red lines, inhibition of transcription; solid black arrow, phosphorylation; P, phosphate; dashed arrow, reaction catalyzed by Pbs2.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Park BJ, Wannemuehler KA, Marston BJ, Govender N, Pappas PG, Chiller TM. Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS. Aids. 2009;23:525–530. - PubMed
    1. Sanfelice F. Contributo alla morfologia e biologia dei blastomiceti che si sviluppano nei succhi de alcuni frutti. Ann Ist Ig R Univ Roma. 1894;4:463–469.
    1. Busse O. Uber parasitare Zelleinschlusse und ihre Zuchtung. Centralbl Bakt Parasit. 1894:16.
    1. Klutts JS, Doering TL. Cryptococcal xylosyltransferase 1 (Cxt1p) from Cryptocooccus neoformans plays a direct role in the synthesis of capsule polysaccharides. J Biol Chem. 2008;283:14327–14334. - PMC - PubMed
    1. Klutts JS, Yoneda A, Reilly MC, Bose I, Doering TL. Glycosyltransferases and their products: cryptococcal variations on fungal themes. FEMS Yeast Res. 2006;6:499–512. - PubMed

Publication types

MeSH terms

LinkOut - more resources

-