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Infection and Immunity, July 2009, p. 3014-3022, Vol. 77, No. 7
0019-9567/09/$08.00+0     doi:10.1128/IAI.01511-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Listeria monocytogenes 6-Phosphogluconolactonase Mutants Induce Increased Activation of a Host Cytosolic Surveillance Pathway{triangledown}

Gregory T. Crimmins,1,{dagger} Michael W. Schelle,2 Anat A. Herskovits,1,{ddagger} Peggy P. Ni,1,§ Benjamin C. Kline,1 Nicole Meyer-Morse,1 Anthony T. Iavarone,3 and Daniel A. Portnoy1,4*

Department of Molecular and Cell Biology,1 Department of Chemistry,2 QB3/Chemistry Mass Spectrometry Facility,3 School of Public Health, University of California, Berkeley, California 947204

Received 12 December 2008/ Returned for modification 23 January 2009/ Accepted 10 April 2009

Infection with wild-type Listeria monocytogenes activates a host cytosolic surveillance response characterized by the expression of beta interferon (IFN-β). We performed a genetic screen to identify L. monocytogenes transposon insertion mutants that induced altered levels of host IFN-β expression. One mutant from this screen induced elevated levels of IFN-β and harbored a Tn917 insertion upstream of lmo0558. This study identified lmo0558 as the 6-phosphogluconolactonase gene (pgl), which encodes the second enzyme in the pentose phosphate pathway. pgl mutant L. monocytogenes accumulated and secreted large amounts of gluconate, likely derived from labile 6-phosphogluconolactone, the substrate of Pgl. The pgl deletion mutant had decreased growth in glucose-limiting minimal medium but grew normally when excess glucose was added. Microarray analysis revealed that the pgl deletion mutant had increased expression of several β-glucosidases, consistent with known inhibition of β-glucosidases by 6-phosphogluconolactone. While growth in macrophages was indistinguishable from that of wild-type bacteria, pgl mutant L. monocytogenes exhibited a 15- to 30-fold defect in growth in vivo. In addition, L. monocytogenes harboring an in-frame deletion of pgl was more sensitive to oxidative stress. This study identified L. monocytogenes pgl and provided the first link between the bacterial pentose phosphate pathway and activation of host IFN-β expression.

* Corresponding author. Mailing address: University of California, Berkeley, Department of Molecular and Cell Biology and School of Public Health, 508 Barker Hall no. 3202, Berkeley, CA 94720-3202. Phone: (510) 643-3925. Fax: (510) 643-6334. E-mail: portnoy{at}berkeley.edu

{triangledown} Published ahead of print on 27 April 2009.

Editor: V. J. DiRita

{dagger} Present address: Department of Molecular Biology and Microbiology, Tufts University, Boston, MA.

{ddagger} Present address: Department of Molecular Microbiology and Biotechnology, Tel-Aviv University, Tel-Aviv, Israel.

§ Present address: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO.

Infection and Immunity, July 2009, p. 3014-3022, Vol. 77, No. 7
0019-9567/09/$08.00+0     doi:10.1128/IAI.01511-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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