Listeria monocytogenes 6-Phosphogluconolactonase Mutants Induce Increased Activation of a Host Cytosolic Surveillance Pathway
| Autor: | Benjamin C. Kline, Michael W. Schelle, Gregory T. Crimmins, Anat A. Herskovits, Peggy P. Ni, Nicole Meyer-Morse, Daniel A. Portnoy, Anthony T. Iavarone |
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| Rok vydání: | 2009 |
| Předmět: |
Virulence Factors
Immunology Mutant Colony Count Microbial Virulence Pentose phosphate pathway Biology medicine.disease_cause Gluconates Microbiology Mice Listeria monocytogenes medicine Animals Cellulases Listeriosis Cells Cultured 6-phosphogluconolactonase Oligonucleotide Array Sequence Analysis chemistry.chemical_classification Host Response and Inflammation Mutation Macrophages Interferon-beta Up-Regulation Mice Inbred C57BL Mutagenesis Insertional Oxidative Stress Glucose Infectious Diseases Enzyme Liver chemistry DNA Transposable Elements Parasitology Carboxylic Ester Hydrolases Gene Deletion Spleen Genetic screen |
| Zdroj: | Infection and Immunity. 77:3014-3022 |
| ISSN: | 1098-5522 0019-9567 |
| DOI: | 10.1128/iai.01511-08 |
| Popis: | 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 Tn 917 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. |
| Databáze: | OpenAIRE |
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