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Infection and Immunity, December 1998, p. 5930-5938, Vol. 66, No. 12
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Phosphatidylcholine-Specific Phospholipase C from Listeria monocytogenes Is an Important Virulence Factor in Murine Cerebral Listeriosis

Dirk Schlüter,1,* Eugen Domann,2 Christine Buck,3 Torsten Hain,2 Herbert Hof,1 Trinad Chakraborty,2 and Martina Deckert-Schlüter3

Institut für Medizinische Mikrobiologie und Hygiene, Universitätsklinikum Mannheim, Universität Heidelberg, Mannheim,1 Institut für Medizinische Mikrobiologie, Justus-Liebig-Universität Gießen, Gießen,2 and Institut für Neuropathologie, Universitätskliniken Bonn, Bonn,3 Germany

Received 8 July 1998/Returned for modification 18 August 1998/Accepted 25 September 1998

Meningoencephalitis is a serious and often fatal complication of Listeria monocytogenes infection. The aim of the present study was to analyze the role of internalin A (InlA) and B, which are involved in the invasion of L. monocytogenes into cultivated host tissue cells, and that of phosphatidylcholine-specific phospholipase C (PlcB), which mainly promotes the direct cell-to-cell spread of L. monocytogenes, in murine cerebral listeriosis by use of an InlA/B (Delta inlAB2)- and a PlcB (Delta plcB2)-deficient isogenic deletion mutant strain and the wild-type (WT) L. monocytogenes EGD. Listeria strains were directly applied to the brain, a technique which has been employed previously to study the pathogenesis of cerebral listeriosis (D. Schlüter, S. B. Oprisiu, S. Chahoud, D. Weiner, O. D. Wiestler, H. Hof, and M. Deckert-Schlüter, Eur. J. Immunol. 25:2384-2391, 1995). We demonstrated that PlcB, but not InlA or InlB, is an important virulence factor in cerebral listeriosis. Nonimmunized mice infected intracerebrally with the Delta plcB2 strain survived significantly longer and had a reduced intracerebral bacterial load compared to mice infected with the Delta inlAB2 strain or WT bacteria. In addition, immunization with the WT prior to intracerebral infection significantly increased the survival rate of mice challenged intracerebrally with the Delta plcB2 strain compared to that of mice infected with the WT or Delta inlAB2 strain. Histopathology revealed that the major difference between the various experimental groups was a significantly delayed intracerebral spread of the Delta plcB2 mutant strain, indicating that cell-to-cell spread is an important pathogenic feature of cerebral listeriosis. Interestingly, irrespective of the Listeria mutant used, the apoptosis of hippocampal and cerebellar neurons and an internal hydrocephalus developed in surviving mice, indicating that these complications are not dependent on the virulence factors InlA/B and PlcB. In conclusion, this study points to PlcB as a virulence factor important for the intracerebral pathogenesis of murine L. monocytogenes meningoencephalitis.

* Corresponding author. Mailing address: Institut für Medizinische Mikrobiologie und Hygiene, Universitätsklinikum Mannheim, Universität Heidelberg, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany. Phone: (49) 621/383-2036. Fax: (49) 621/383-3816. E-mail: dirk.schlueter{at}imh.ma.uni-heidelberg.de.

Infection and Immunity, December 1998, p. 5930-5938, Vol. 66, No. 12
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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