Phosphatidylcholine-specific phospholipase C from Listeria monocytogenes is an important virulence factor in murine cerebral listeriosis.
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 (DeltainlAB2)- and a PlcB (DeltaplcB2)-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 DeltaplcB2 strain survived significantly longer and had a reduced intracerebral bacterial load compared to mice infected with the DeltainlAB2 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 DeltaplcB2 strain compared to that of mice infected with the WT or DeltainlAB2 strain. Histopathology revealed that the major difference between the various experimental groups was a significantly delayed intracerebral spread of the DeltaplcB2 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.
Schlüter
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Institut für Medizinische Mikrobiologie und Hygiene, Universit atsklinikum Mannheim, Universität Heidelberg, Mannheim, Germany. dirk.schlueter@imh.ma.uni-heidelberg.de
Domann
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E
Buck
C
C
Hain
T
T
Hof
H
H
Chakraborty
T
T
Deckert-Schlüter
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M
D000818:Animals; D017209:Apoptosis; D001426:Bacterial Proteins / Q000235:genetics; D001921:Brain / Q000473:pathology; D005260:Female; D017353:Gene Deletion; D005798:Genes, Bacterial; D008089:Listeria monocytogenes / Q000201:enzymology / Q000235:genetics / Q000472:pathogenicity*; D008584:Meningitis, Listeria / Q000209:etiology* / Q000401:mortality / Q000473:pathology; D008590:Meningoencephalitis / Q000209:etiology* / Q000401:mortality / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D010738:Type C Phospholipases / Q000235:genetics
D001426:Bacterial Proteins; C069761:internalin protein, Bacteria; D010738:Type C Phospholipases; C105598:phosphatidylcholine-specific phospholipase C