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Bacteriophages have been shown to influence the evolution of their host and, in several cases, have a major effect on pathogenicity and/or virulence of bacterial pathogens. Several mechanisms allow phages to change the biology and associated phenotypes of their host. This chapter aims at explaining these mechanisms in the context of Listeria evolution and pathogenesis, using examples from other pathogens. Our current knowledge on the biology and applications of a few selected Listeria phages is reviewed and discussed. The lack of evidence for their influence on the phenotype of lysogenized host bacteria likely reflects our fragmentary knowledge about Listeria phages, especially on the molecular level. Clearly, much more research is required to understand the full impact of phages on their hosts, both in an ecological and evolutionary context. [ABSTRACT FROM AUTHOR]

Listeria monocytogenes has long served as a model pathogen for elucidating many functions of the immune response. Both the innate and adaptive immune systems are crucial to the recognition and elimination of this pathogen from the host. However, although L. monocytogenes infection induces robust immune responses, the bacterium has evolved mechanisms to evade and modulate the immune response. Its intracellular niche allows it to evade several aspects of the innate and adaptive immune systems. Expression of different virulence factors during infection leads to modulation of other arms of the immune response. In this chapter, we focus on the specific mechanisms L. monocytogenes has evolved to evade and modulate the host immune response [ABSTRACT FROM AUTHOR]

Listeria monocytogenes has evolved the ability to exploit its host's actin cytoskeleton to power movement within and between cells without exiting from the cell, enabling it to evade the immune response. This remarkable adaptation requires the expression of a single bacterial surface protein, called ActA, that performs two key functions. It activates the host Arp2/3 complex, which promotes the nucleation of actin filaments at the bacterial surface and the organization of filaments into branched networks. Moreover, it recruits host Ena/VASP proteins and profilin, which stimulate actin filament elongation. Together these cellular factors promote the assembly of actin comet tails that recruit additional host cytoskeletal proteins that control filament bundling, terminate polymerization, and promote depolymerization. The assembly of the comet tail is essential for coupling actin polymerization to the force that drives bacterial propulsion. The process of bacterial motility can be reconstituted in vitro, facilitating a relatively complete understanding of the biochemical and biophysical mechanisms of actin polymerization and force generation. This chapter presents a review of the experiments that have led to our current understanding of the molecular mechanisms of L. monocytogenes' motility and spread. [ABSTRACT FROM AUTHOR]

The ability of Listeria monocytogenes to escape from vacuoles of infected cells and subsequently to replicate in the cytosol and spread from cell to cell is one of the distinctive features of this facultative intracellular pathogen. The process of escape is mediated by several proteins that are encoded by genes in the PrfA regulon cluster. These include listeriolysin O, a pore-forming, cholesterol-dependent cytolysin, a phosphatidylinositol-specific phospholipase C (PI-PLC), and a broad range phospholipase whose proteolytic activation is mediated by a metalloprotease. These proteins are described and their specific roles in escape from the vacuole are discussed. [ABSTRACT FROM AUTHOR]

Critical for the pathophysiology of the disease caused by Listeria monocytogenes is the bacterial ability to promote its entry into nonphagocytic cells. Different members of the internalin family of listerial surface proteins have been shown to be required for cellular invasion, subverting cellular functions and structures such as adherens junctions in the case of InlA, or the hepatocyte growth factor receptor signaling in the case of InlB. Additional noninternalin molecules, including the LPXTG-anchored cell wall protein VIP, the glycine/tryptophane-anchored amidases Ami and Auto, and the secreted pore-forming cholesterol-dependent cytolysin listeriolysin O are also necessary for efficient cell entry, revealing the complexity of the bacterial molecular program required for gaining access to the host intracellular environment. [ABSTRACT FROM AUTHOR]

Listeria monocytogenes is a gram-positive bacterium that lives within soil and decaying plant material but is also capable of transitioning into a deadly pathogen following ingestion by mammals. The bacterium makes the transition from outside environment to host via the coordinate regulation of virulence gene products that enable bacterial replication within host cells. PrfA is transcriptional activator that is required for the expression of nearly all identified L. monocytogenes virulence gene products. The expression of the prfA gene and the activity of the PrfA protein are carefully regulated by multiple mechanisms within L. monocytogenes. Two promoters function to provide the initial levels of PrfA that direct bacterial escape from host cell vacuoles, whereas a third promoter contributes to high level expression of prfA to promote spread of intracellular bacteria to adjacent host cells. The synthesis of PrfA protein is temperature-regulated such that prfA mRNA secondary structure prevents protein translation at low temperatures. An additional mechanism of control exists to regulate PrfA activity as PrfA appears to require the binding of a cofactor for full activation. Strains containing PrfA mutant proteins that are locked into a PrfA-activated state are fully virulent in animal models of infection, but are compromised for bacterial fitness outside of the host. It therefore appears that L. monocytogenes must maintain a balance between life in the host and life in the outside environment. Analyses of the L. monocytogenes genome sequence and microarray analysis indicate that additional gene products are subject to PrfA regulation either via direct interaction with PrfA or indirectly as the result of another PrfA-activated factor. [ABSTRACT FROM AUTHOR]

The widespread presence of Listeria monocytogenes in various diverse environments, including those that are natural (i.e., nonagricultural), agricultural, and food-associated, suggests that these environments may serve as sources or reservoirs of L. monocytogenes that can be transmitted to various hosts, including humans. As the vast majority of human listeriosis infections are recognized to occur through consumption of contaminated foods, and as animal listeriosis infections also appear to be predominantly feed-borne, development of effective intervention strategies for reducing the incidence of listeriosis among susceptible human and animal populations requires elucidation of specific routes of L. monocytogenes transmission among different ecosystems and compartments within food and feed production systems. Current knowledge of L. monocytogenes ecology is presented to provide insight into the primary sources that appear to contribute to its introduction into human food-associated environments and foods as well as its transmission among various compartments in food and agricultural production systems. [ABSTRACT FROM AUTHOR]

Compared to the rich wealth of knowledge concerning the molecular basis of Listeria monocytogenes virulence, little is known on the physiological background necessary for allowing this facultative intracellular human pathogen to survive and replicate in its natural surroundings, particularly in the host cell's cytosol. This cellular compartment appears to be the preferred site of replication, during a systemic infection caused by L. monocytogenes. Complementing earlier physiological studies, especially the more recent results obtained by comparative genomics, transcriptome, and proteome analyses, and by 13C-isotopolog perturbation studies, allow us today to draw a first (although still rather incomplete) picture of how the metabolism of these bacteria may function to facilitate efficient growth under extra- and intracellular conditions. In this chapter, we concentrate on the carbon- and nitrogen-metabolism of L. monocytogenes as deduced from these studies. Although many carbon- and nitrogen-metabolic pathways of L. monocytogenes appear to be similar to those of the extensively studied Bacillus subtilis, which like L. monocytogenes belongs to the group of low G+C gram-positive (Gp) bacteria, there seem to be some profound differences that are essential for understanding the interplay of the listerial metabolism with that of the host cells and hence may have an important impact on listerial virulence. [ABSTRACT FROM AUTHOR]

The publication of the complete genome sequences of four clinical Listeria monocytogenes isolates and one of its apathogenic relative, Listeria innocua, in 2001 and 2003 has paved the way for major breakthroughs in understanding the biology of L. monocytogenes. The availability of these sequences allowed applying postgenomics analysis to understand virulence and ecology of L. monocytogenes and evolution of the genus Listeria. Comparative genomics now help to unravel the molecular basis of the pathogenesis, the host range, the evolution, and the phenotypic differences among L. monocytogenes isolates and within the genus Listeria. Based on sequence analysis, many new virulence factors have been identified, foremost among them, surface proteins like internalins, in agreement with the expansion of this protein family revealed by genome sequencing. The discovery of a broad transport capacity, in particular, of carbon sources and of unexpected metabolic pathways like the biosynthesis of vitamin B12 and glutathione (GSH) explains the ubiquitous nature of Listeria. Some of the many regulators identified in the genome are now analyzed, demonstrating, e.g., the importance of an orphan two-component regulator DegU in virulence of L. monocytogenes or leading to the identification of a new class of regulators like MogR, the master regulator of flagella expression. Combined with genome analysis, transcriptome studies using microarrays allow for the first time the global and parallel analysis of L. monocytogenes gene expression inside and outside eukaryotic cells. Multiple ongoing sequencing projects allowing multigenome comparisons combined with different postgenomics and functional analyses open the way to a global understanding of the ability of Listeria to adapt to a broad range of environments and hosts and of the multiple aspects of the disease it causes, listeriosis. [ABSTRACT FROM AUTHOR]