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INTRODUCTION

Listeria monocytogenes is a food-borne pathogen that can cause serious infections, particularly in pregnant women and immunocompromised individuals. A ubiquitous saprophytic environmental bacterium, L. monocytogenes is also a facultative intracellular pathogen with a broad host range. Humans are probably accidental hosts for this microorganism. L. monocytogenes is of interest not only to clinicians but also to basic scientists as a model intracellular pathogen that is used to study basic mechanisms of microbial pathogenesis and host immunity.

MICROBIOLOGY

L. monocytogenes is a facultatively anaerobic, nonsporulating, gram-positive rod that grows over a broad temperature range, including refrigeration temperatures. This organism is motile during growth at low temperatures but much less so at 37°C. The vast majority of cases of human listerial disease can be traced to serotypes 1/2a, 1/2b, and 4. L. monocytogenes is weakly β-hemolytic on blood agar, and (as detailed below) its β-hemolysin is an essential determinant of its pathogenicity.

PATHOGENESIS

Infections with L. monocytogenes follow ingestion of contaminated food that contains the bacteria at high concentrations. The conversion from environmental saprophyte to pathogen involves the coordinate regulation of bacterial determinants of pathogenesis that mediate entry into cells, intracellular growth, and cell-to-cell spread. Many of the organism’s pathogenic strategies can be examined experimentally in tissue culture models of infection (Fig. 48-1). Like other enteric pathogens, L. monocytogenes induces its own internalization by cells that are not normally phagocytic. Its entry into cells is mediated by host surface proteins classified as internalins. Internalin-mediated entry is important in the crossing of intestinal, blood-brain, and fetoplacental barriers, although how L. monocytogenes traffics from the intestine to the brain or fetus is only beginning to be investigated. In a pregnant guinea pig model of infection, L. monocytogenes was shown to traffic from maternal organs to the placenta; surprisingly, however, it also trafficked from the placenta back to maternal organs. These data are consistent with a model in which miscarriage can be viewed as a host defense strategy to eliminate a nidus of infection.

FIGURE 48-1

Stages in the intracellular life cycle of Listeria monocytogenes. The central diagram depicts cell entry, escape from a vacuole, actin nucleation, actin-based motility, and cell-to-cell spread. Surrounding the diagram are representative electron micrographs from which it was derived. ActA, surface protein mediating nucleation of host actin filaments to propel bacteria intra- and intercellularly; LLO, listeriolysin O; PLCs, phospholipases C; Inl, internalin. See text for further details. (Adapted with permission from LG Tilney, DA Portnoy: J Cell Biol 109:1597, 1989. © Rockefeller University Press.)

An essential determinant of the pathogenesis of L. monocytogenes is its β-hemolysin, listeriolysin O (LLO). LLO is a pore-forming, cholesterol-dependent cytolysin. (Related cytolysins include streptolysin O, pneumolysin, and perfringolysin O, all of which are produced by extracellular pathogens.) LLO is ...

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