Infection begins with the inhalation of the Legionella pneumophila bacterium. Once the Legionella reach the alveoli they come in contact with an alveolar macrophage. This only takes place, however, if the bacteria are virulent enough to overpower the host immune response. After the bacteria reach the alveolar macrophage, coiling phagocytosis begins, and the macrophage takes the bacteria into a food vacuole inside the cell. Here, Legionella stops the fusion of the monocyte and the lysosome. As a result, the bacteria are able to multiply inside the macrophage, where they eventually lyse the cell and infect other cells4.
Methods for discovering the virulence factors of Legionella pneumophila have taken scientists a very long time to isolate, because of the difficulty in colonizing this bacteria in a laboratory environment. Although, none of the virulence factors found have been completely proven, these are a few that scientists have thought to exist6.
There are three known virulence genes encoded in Legionella pneumophila that have recently been discovered. These are as follows: the Icm genes, the mip genes, and the ompS gene. The Icm genes have been found to be necessary for the intracellular multiplication of Legionella. The mip genes or in full term, the macrophage infectivity potentiator, are responsible for increasing Legionella infection. Finally the ompS gene has been determined to be the gene for the major outer membrane protein (MOMP). This gene therefore is extremely important in the binding of Legionella to macrophages, which stimulates coiling phagocytosis2. The question that many people have is how are these bacterial genes regulated? How does the Legionella organism know when it has entered a phagosome inside the cell as a cue for intracellular multiplication and the expression of the Icm genes? More research still has to be done on both of these questions, however, scientists have a few ideas. They feel that the result is a 2-component signal transduction pathway that regulates gene control. For example, an outer membrane protein sends a message to an intracellular protein in response to some sort of extracellular stimuli. Then, these proteins which are inside the cell regulate the gene transcription as well as the expression of the bacteria2.
This process begins with the attachment of the bacteria to the phagocyte. Attachment takes place via opsonization, where both the complement components C3b and C3bi are involved. C3b and C3bi covalently modify and attach to the major outer membrane protein (MOMP) which is encoded by the ompS gene1. Once this takes place the bacteria are able to to bind to the complement receptors CR1 and CR3. With this taking place, coiling phagocytosis is promoted.
Coiling Phagocytosis is a form of phagocytic uptake where a long thin pseudopod is formed and engulfs the bacterium in a coiled vesicle4. This vesicle, however, does not acidify and therefore the fusion of the phagolysosome is inhibited. As a result the bacteria have figured a way that enables them to protect themselves and multiply within this vesicle. Eventually the surface of the vesicle becomes studded with ribosomes. Because of the formation of this species-specific sort of phagosome, scientists have chosen to name it LSP or Legionella-specific phagosome4.
Soon after the formation of the LSP the bacteria inside begin to replicate. In most cases there is a "lag time" of about six to eight hours after infection before one can notice an actual increase in the amount of bacteria. This is probably because the bacteria are accustoming themselves to the conditions inside the LSP. Once the bacteria do begin replicating intracellularly, they have a generation time of about two hours4. This concludes that their nutritional needs are met inside the LSP. The best environment for the bacteria inside the LSP would be a balance of cysteine and iron, free amino acids such as proline, serine, and threonine, a pH near neutral and finally an environment free of Na4.
Scientists are still unaware on the exact method of host cell killing by Legionella pneumophila. Several theories exist on this topic however. The first theory is called bacteria induced apoptosis. This is another way of saying that the presence of the bacteria induce cell death in the host. Another theory on this idea is that there is a burden put on the host cell because of the replication of the Legionella. For example, the bacteria produce NH3 from amino acid metabolism as well as other byproducts of metabolism. These byproducts can cause the host cells to die4.
Legionella pneumophila causes lung damage in many different ways. The first way is by continuously attracting phagocytes and T cells to the infected area. By attracting these protective devices the lung becomes damaged because the phagocytes and T cells release cytokines and other toxic products which do not kill the bacteria but damage the lung. The reason Legionella survive is because it is thought that they release enzymes such as acid phosphatase, phospholypase C, protein kinases, and superoxide dismutase that enhance their survival rate. Another way in which Legionella pneumophila damage lung tissue is by producing extracellular proteases. An example of an extracellular protease is zinc metalloprotease. This protease is very similar structurally to an elastase which has been found to cause severe lung damage in cystic fibrosis patients. This protease has been know to produce hemolytic activity, resulting in lesion formation in lung tissue4.
