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About Legionella

General information:
Non-spore-forming, Gram-negative bacilli, a member of the γ-proteobacteria, and so far, 42 species and 65 serogroups of Legionellae have been described.
Intracellular replication within selected host cells is the primary and perhaps sole means of proliferation in the environment.
Many of these species are reported to be pathogenic for humans, but L. pneumophila is the most frequently isolated species associated with disease.
Characteristics:
Dual host system
allowing intrcellular growth in protozoa, such as Acanthamoeba castellanii, Hartmanella sp. or Naeglaria sp., and in human alveolar macrophages. Protozoa are essential for the growth of Legionella and the interaction with amoeba seems to generate a pool of virulence traits during evolution.
Intracellular pathogen
invades and replicates within a protective phagosome inside alveolar macrophages.
Two phase of growth
replicative phase -- sodium resistance, non-flagellated, low cytotoxicity
infectious phase -- short, thick, flagellated and highly cytoxicity.
Killing and lysis of macrophages require two steps
trigger apoptosis at early stage
induce pore formation later.
The key to L. pneumophila's virulence is its ability to prevent phagosome-lysosome fusion.
The genome sequences of L. pneumophila contains a large number of genes encoding proteins that show high similarity to eukaryotic proteins or motifs known to be involved in protein-protein interactions, which are present either solely or primarily in eukaryotes, suggesting that L. pneumophila may have acquired specific mechanisms of cross-talk with its eukaryotic hosts.
A particularly high number and wide variety of secretion systems presented in L. pneumophila genome.
Disease:
Legionnaires' Disease.
Selected genomes:comparative pathogenomics
L. longbeachae NSW150, 4077332 bp, NC_013861
L. pneumophila str. Corby, 3576470 bp, NC_009494
L. pneumophila str. Lens, 3345687 bp, NC_006369
L. pneumophila str. Paris, 3503610 bp, NC_006368
L. pneumophila subsp. pneumophila str. Philadelphia 1, 3397754 bp, NC_002942
Related publications:
Chien M, et al., 2004. The genomic sequence of the accidental pathogen Legionella pneumophila. Science 305(5692):1966-1968.
Cazalet C, et al., 2004. Evidence in the Legionella pneumophila genome for exploitation of host cell functions and high genome plasticity. Nat. Genet. 36(11):1165-1173.
Glockner G, et al., 2008. Identification and characterization of a new conjugation/type IVA secretion system (trb/tra) of Legionella pneumophila Corby localized on two mobile genomic islands. Int J Med Microbiol 298(5):411-428.
Cazalet C, et al., 2010. Analysis of the Legionella longbeachae genome and transcriptome uncovers unique strategies to cause Legionnaires' disease. PLoS Genet 6(2):e1000851.
Figures:
Schema for L. pneumophila pathway in macrophages (Reproduced from: Swanson MS, Hammer BK, 2000. Legionella pneumophila pathogesesis: a fateful journey from amoebae to macrophages. Annu. Rev. Microbiol. 54:567-613.).


Major virulence factors in Legionella:
Adherence
Hsp60
MOMP (Major outer membrane protein)
Type IV pili
Effector delivery system
Dot/Icm (Defect in organella trafficking/intracellular multiplication)
Dot/Icm T4SS secreted effectors
LigA (L. pneumophila infectivity gene)
lsp T2SS (Type II secretion system)
Motility
Flagella
Exotoxin
RtxA
Immune modulation
LPS
Nutritional/Metabolic factor
CcmC
FeoAB
FrgA (Fur regulated gene)
IraAB
Legiobactin
Pht (Phagosomal transporter)
Stress survival
GspA (Global stress gene)
KatAB
SodB
SodC
Post-translational modification
Mip (Macrophage infectivity potentiator)
Regulation
CsrA
LetA/S
RelA
RpoS
Others
Enh loci (Enhanced entry)
PmiA (Protozoa and macrophage infectivity loci protein)

Genomic location of virulence-related genes in Legionella:


Reported anti-virulence compounds to Legionella:
Benzenoids
Phenols
Lipids and lipid-like molecules
Prenol lipids
Organoheterocyclic compounds
Benzothiazines
Diazinanes
Diazines
Indoles and derivatives
Phenylpropanoids and polyketides
Coumarins and derivatives

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