ABSTRACT
Listeria monocytogenes is a multisystemic invasive pathogen capable of colonizing multiple host tissues, causing a range of clinical conditions. Some of these conditions, namely meningoencephalitis and abortion, are much more common than others, reecting the specic tropism L. monocytogenes has for the brain and the placenta. In most cases, the clinical manifestations of listeriosis occur in debilitated, immunocompromised individuals and therefore L. monocytogenes can be considered as an opportunistic pathogen. L. monocytogenes is also a multihost pathogen capable of infecting and
4.1 Introduction ...........................................................................................................................97 4.1.1 Clinical Manifestations ..............................................................................................98 4.1.2 Physiopathogenesis ....................................................................................................99 4.1.3 Factors Affecting the Outcome of Listeria Infection .............................................. 101
4.2 Molecular Determinants of Virulence Involved in the Intracellular Life Cycle ................ 102 4.2.1 The Cell Biology of Infection .................................................................................. 102 4.2.2 Surface Proteins of the Internalin Family and the Invasion of Nonprofessional
Phagocytic Cells....................................................................................................... 104 4.2.3 Other Surface Proteins Involved in Host Cell Invasion ........................................... 106
4.2.3.1 p60 and Related Proteins............................................................................ 106 4.2.3.2 The Surface Proteins ActA, LpeA, FbpA, LAP, and Vip .......................... 107
4.2.4 Secreted Membrane-damaging Proteins Allowing Escape from the Phagocytic Vacuole ..................................................................................................................... 108 4.2.4.1 Listeriolysin O ............................................................................................ 108 4.2.4.2 Phospholipases and Metalloprotease .......................................................... 110 4.2.4.3 Other Factors .............................................................................................. 112
4.2.5 Nutritional and Metabolic Determinants of Cytosolic Replication ......................... 112 4.2.6 The Surface Protein ActA and Its Role in Actin-Based Motility and Cell-to-
Cell Spread ............................................................................................................... 113 4.3 Molecular Determinants Involved in Colonization of the Host .......................................... 117
4.3.1 Bile Salt Hydrolase .................................................................................................. 117 4.3.2 Vitamin B12 Biosynthesis and Anaerobic Use of Ethanolamine .............................. 118 4.3.3 Stp Serine-Threonine Phosphatase .......................................................................... 118 4.3.4 The Peptidoglycan N-deacetylase PgdA .................................................................. 118
4.4 Regulation of Virulence ...................................................................................................... 119 4.4.1 The PrfA Regulon .................................................................................................... 120 4.4.2 PrfA Regulation Mechanisms and Modulatory Signals .......................................... 120 4.4.3 Other Regulatory Systems ....................................................................................... 122
4.5 Conclusions and Perspectives .............................................................................................124 Acknowledgments ..........................................................................................................................124 References ......................................................................................................................................124
