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Infection and Immunity, October 2007, p. 4769-4779, Vol. 75, No. 10
0019-9567/07/$08.00+0 doi:10.1128/IAI.00536-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.
Mutant
Section of Infectious Diseases, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois,1 Jesse Brown VA Medical Center, Chicago, Illinois2
Received 14 April 2007/ Returned for modification 18 May 2007/ Accepted 15 July 2007
Mannan binding lectin (MBL) is an innate immune mediator belonging to the collectin family known to bind to the surfaces of many viruses, bacteria, and fungi. However, pathogenic strains of the fungus Cryptococcus neoformans are resistant to MBL binding. To dissect the mechanism of cryptococcal resistance to MBL, we compared MBL binding to an encapsulated wild-type strain, an encapsulated ccr4
mutant defective in cell integrity, and an acapsular cap60
strain. No MBL binding was detected on wild-type C. neoformans. In contrast, the ccr4
mutant bound MBL to the cell wall, predominantly at the ends of enlarged buds, whereas the acapsular strain bound MBL only at the bud neck and bud scars. In addition, the ccr4
mutant was sensitive to the cell wall-active antifungal caspofungin and other cell wall stress inducers, and its virulence was reduced in a mouse model of cryptococcosis. Interestingly, treatment of wild-type cells with caspofungin also increased MBL binding to C. neoformans. These results suggest that both the presence of capsule and wild-type cell wall architecture preclude MBL binding to C. neoformans.
Published ahead of print on 23 July 2007.
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