Intracellular Life Cycle

The broad protozoal host spectrum of Legionella and the exploitation of basic cellular mechanisms of eukaryotes enables Legionella to replicate within human cells. Striking similarities in both host systems include the uptake by phagocytosis, the formation of a Legionella-specific vacuole that does not follow the endosomal pathway, the association of this vacuole with ribosome-studded membranes that originate from the endoplasmic reticulum, and finally, host cell lysis. In this life cycle, Legionella switches from a nonreplicating, flagellated, stress-resistant, cytotoxic phase (transmission form) to a replicating, nonflagellated phase (growth form). The conversion is triggered by a stringent response-like mechanism.[2]

In recent years, much progress has been made toward the characterization of how Legionella infects host cells. Because the reprogramming of the endocytic pathway occurs between the initial attachment and the replicative phase of the bacteria, it is highly likely that cell surface components and secreted factors are involved in this process. Various surface structures including the major outer membrane protein (MOMP), which mediates the uptake of Legionella via the CR1 and CR3 receptors of macrophages, the type IV pilus biogenesis, and the macrophage infectivity potentiator (Mip) protein have been characterized. Moreover, the Dot/Icm secretion system plays a pivotal role during infection. Yet, unidentified factors that are injected into host cells by this type IV secretion system obviously prevent the Legionella-containing vacuole from endosomal maturation. Recently, macrophage-specific virulence genes such as mil (macrophage-specific infectivity loci) and protozoa specific virulence genes such as legionella infectivity gene (ligA), type II secretion system (lsp), alternative sigma factors (rpoS) have been identified. This suggests that besides many similarities, notable differences in the mechanisms of entering and exiting the host cell exist.[3]

Comparison of the nucleotide sequence of different Legionella species revealed 23% nucleotide sequence variation within the 16S rRNA gene and 56% variation for the mip gene. However, knowledge of genetic diversity between different isolates of the same or of different Legionella species is still very limited. The current Legionella genome project (http://genome3.cpmc.columbia. edu/~legion/) may soon reveal the relation between the presence of specific genes and the prevalence of certain species in epidemiological investigations.1-4-1

In order to study the host side of infection, guinea pigs, primary cell culture systems, and cell lines derived from human leukemias such as U937, HL60, HeLa, Vero, and McCoy cells have been used. In addition, the infection of axenically grown protozoa such as Acanthamoeba, Hartmannella, and Naegleria have increased our knowledge about the ecology of Legionella.[5] Especially, the haploid soil amoeba Dictyostelium discoideum has proven to be a suitable model system for studying cellular mechanisms of pathogenesis. This surrogate host system is amenable to genetic manipulation and evolutionarily expresses highly conserved cellular markers. In the future, the combination of full-scale genomic sequencing and high-throughput expression analysis with Legionella and Dictyostelium should reveal important aspects of the pathogen-host cross-talk.[6,7]

Getting Started With Dumbbells

Getting Started With Dumbbells

The use of dumbbells gives you a much more comprehensive strengthening effect because the workout engages your stabilizer muscles, in addition to the muscle you may be pin-pointing. Without all of the belts and artificial stabilizers of a machine, you also engage your core muscles, which are your body's natural stabilizers.

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