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Infection and Immunity, June 2009, p. 2447-2454, Vol. 77, No. 6
0019-9567/09/$08.00+0     doi:10.1128/IAI.01345-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Secreted Dipeptidyl Peptidase IV Activity in the Dimorphic Fungal Pathogen Histoplasma capsulatum{triangledown}

Kendal G. Cooper and Jon P. Woods*

Department of Medical Microbiology and Immunology, University of Wisconsin, Madison, Wisconsin 53706

Received 3 November 2008/ Returned for modification 2 December 2008/ Accepted 26 March 2009

Dipeptidyl peptidase type IV (DppIV) enzymes are broadly distributed phylogenetically and display diverse functions, including intercellular signaling, immunomodulation, protein maturation and processing, metabolism, and nutrient acquisition. We identified a secreted proteolytic activity in Histoplasma capsulatum effective toward DppIV-specific substrates. In order to determine the gene(s) that encodes this activity, we identified two putative DPPIV homologs (HcDPPIVA and HcDPPIVB) in H. capsulatum based on a homology search with Aspergillus fumigatus DppIV. Comparative sequence analysis revealed that HcDppIVA is similar to secreted DppIV enzymes, while HcDppIVB clusters with intracellular DapB-like enzymes. Unexpectedly, silencing of HcDPPIVA by RNA interference (RNAi) had no effect on secreted DppIV activity and an HcDPPIVA-null deletion mutant also showed no abrogation of secreted DppIV activity. In contrast, RNAi silencing of HcDPPIVB significantly reduced the level of secreted DppIV activity. RNAi silencing of HcDPPIVB in the HcDPPIVA-null mutant had no additional effect on secreted DppIV activity, indicating that HcDPPIVA does not contribute to secreted activity. RNAi silencing of HcDPPIVB did not affect the ability to kill a murine macrophage-like cell line, RAW 264.7, indicating that this gene is not required for infection of macrophages.

* Corresponding author. Mailing address: Department of Medical Microbiology and Immunology, 5325 Microbial Sciences Building, University of Wisconsin, 1550 Linden Dr., Madison, WI 53706. Phone: (608) 265-6292. Fax: (608) 265-6717. E-mail: jpwoods{at}wisc.edu

{triangledown} Published ahead of print on 6 April 2009.

Editor: A. Casadevall

Infection and Immunity, June 2009, p. 2447-2454, Vol. 77, No. 6
0019-9567/09/$08.00+0     doi:10.1128/IAI.01345-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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