Introduction:

Legionella pneumophila is an intracellular gram-negative bacillus that causes acue febrile pneumonia (Legionnaires’ disease).

Legionella is composed of 48 different species and 70 different serotypes, although L. pneumophila accounts for the vast majority of huma infections (>90%), with other species such as Legionella longbeachae, Legionella bozmanii, and Legionella micdadei being isolated for less commonly.

The incidence of Legionella infections is not know precisely, but it is estimated that from 6% to 15% of all pneumonias requiring hospitalization are due to these organsisms.

Legionella appear pleomorphic, thin,. They do not stain well with common reagents but can be stained with Deiterle silver stain. They cause Pontiac fever as well as a severe form of pneumonia called Legionnaires’ disease. Legionella are facultative intracellular parasites, capable of multiplication in alveolar macrophages and monocytes.

Serogroups: 

Legionella pneumophila is the most common pathogenic species, with 15 serogroups described. L pneumophila serogroup 1 accounts for most culture confirmed cases of legionellosis. Legionella pneumophila serogroup 1 is estimated to cause 70% to 90% of reported human legionellosis.  Non-serogroup 1 causes only about 7% of legionellosis cases. L. pneumophila serogroups 1, 3, 4, and 6 cause most human infections. (In general, the DNA relatedness between strains within the same species is 70% o r more. Strains that are closely related by DNA hybridization to a previously recognized species, but that fail to react to antisera against that species, are considered to be new serogroups.)

Transmission:

Pulmonary infection with L. pneumophila usually occurs by direct inhalation of contaminated aerosols and aspiration. The bacteria are commonly present in natural bodies of water such as lakes and streams, air conditioning cooling towers and condensers. Lp is ubiquitous in the acquatic environment, where the bacterium invades and replicates with protozoa.

In most cases, L. pneumophila pneumonia is attributed to inhaling contaiminated aerosols produced by cooling towers, showeres and nebulizers. Aspiration is also a possible mechnism of transmission.

The immunosuppressed are at greatest risk for the disease. Treatment with corticosteroids is a particular risk factor for nosocomial acquisition of legionellosis and possibly because of this, infection with Legionella appears to have a predilection for trasplantation recipients.

Hot tubs can be a source of Legionella growth and transmission when they are inadequately maintained and operated. See CDC

 Pathology:

Mononuclear phagocytes in the respiratory tract (i.e., alveolar macrophages) are regarded as a critical component of the first-line host defense against Legionella infection. In addition to the innate immune response to the microorganism, the importance of adoptive cellular immunity, especially that mediated by CD4+ T cells is underscored by the clinical observation that Legionnaires’ disease is ofted contracted by individuals with depressed cell-mediated immunity, including transplant recipients, patients receiving corticosteroids, and patients suffering from AIDS. 

How Lp avoids Immune Response: (Santic 2005, Infect. Immun. 73: 3166). The Dot/Icm TFSS is essential for integrity of the phagosome. The Dot/Icm system secretes some unknown factor.

Virulence Factors: Virulence facts include –several adhesions called MOMP and MIP, –factors that inhibit phagosome lysosome fusion and –mannose containing surface proteins that trigger cytokine production. 

How Cultures: Legionellae are fastidious organisims that are not readily recovered from routine diagnostic media. The medium most commonly used for isolation of legionellae is buffered charcoal yeast extract (BCYE) agar. 

Diagnosis is by –antigen detection (ELISA, RIA, etc), –serology (antibody titers of 256 or higher are evidence) –as well as morphology and culture characteristics above. 

Upon entry into host cells, Legionella modulates phagosome transport to prevent the formation of degradative phagolysosome. As they are transported, phagosomes containing Legionella associate with vesicles exiting the ER and are converted into a ribosome-lined organelle that supports intracellular replication. The ability of Legionella to evade transport to lysosomes and create an ER derived vacuole requires a bacterial protein secretion apparatus encoded by the dot and icm genes. The Dot-Icm secretion system injects bacterial proteins into eukaryotic host cells during infection that direct transport of Legionella-containing phagosomes to the ER. Legionella mutants defective in this dot/icm encoded secretion system do not replicate intracellularly because they are unable to modulate phagosome transport and reside in conventional phagosomes that are rapidly transported to lysosomes.

Cell Entry: uses  to enter the cell.

Involvement of apoptosis: Molmeret et al, 2004, Cell Microbiol, 6:33. Cleaveage of Rabaptin-5 may involve preventing of fusion.  (Abu-Zant et al, 2005, Infect. Immun. 73:5339) There is robust activation of caspase 3, but no apoptosis, suggesting blocking of apoptosis. Even with inducement of of apoptosis with staurosporine, infected cells are resistant to apoptosis. By microarray, showed anti-apoptotic genes induced in anti-apoptotic genes.At early in stage infection. apoptosis delayed (12-14 hours) during stage Lp needs to get out of cell. This corresponds with upregulation of anti-apoptotic genes.

Animal Models: 

A/J mice strains Lp grows well but all other mice strains clear Lp. For example, Legionella infected macrophages of BALB/c mice (growth restrictive), but not in the macrophages of A/J mice (growth-permissive).