LEGIONELLA - World Health Organization

Once Legionella enters the lung of an infected person (whether by aerosol or aspiration), both
virulent and non-virulent strains are phagocytosed by alveolar macrophages and remain
intact inside the phagocytes. However, only virulent strains can multiply inside the phagocytes
and inhibit the fusion of phagosomes with lysosomes (Horwitz, 1993). This leads to death of
the macrophage and the release of large numbers of bacteria from the cell. The bacteria can
then infect other macrophages, thereby amplifying bacterial concentrations within the lungs.
The pathogenesis of L. pneumophila has been made clearer by the identification of genes that
allow the organism to bypass the endocytic pathways of both protozoan and human cells,
although not all species investigated have this ability. Ogawa et al. (2001) studied six species
of Legionella in Vero cells (a cell line developed from African green monkey nephrocytes). All
species differed in morphology, implying that Legionella species may differ in their mode of
intracellular multiplication.
During phagocytosis, legionellae initiate a complex cascade of activities, including:
• inhibition of the oxidative burst
• reduction in phagosome acidification
• blocking of phagosome maturation
• changes in organelle trafficking.
Legionellae thus prevent bactericidal activity of the phagocyte, and transform the phagosome
into a niche for their replication (Stout & Yu, 1997; Sturgill-Koszycki & Swanson, 2000;
Fields, Benson & Besser, 2002). The organisms can leave the host cell after temporal poreformation-mediated
lysis (Molmeret & Abu Kwaik, 2002) or can remain within an encysted
amoeba (Rowbotham, 1986).
Two growth phases were described for one strain of intracellular L. pneumophila: the replicative
non-motile form and the non-multiplicative motile form (Fields, Benson & Besser, 2002).
Intracellular changes, such as host cell amino acid depletion and the subsequent accumulation
of guanosine 3’, 5’-bispyrophosphate (ppGpp) (Hammer & Swanson, 1999) resulted in the
expression of stationary-phase proteins in one strain of L. pneumophila (although these findings
may not apply to all strains), as shown in Figure 1.1. The proteins produced facilitate the
infection of new host cells, affecting factors such as sodium sensitivity, cytotoxicity, osmotic
resistance, motility and evasion of phagosome–lysosome fusion (Swanson & Hammer, 2000).
The ability to infect host cells is also influenced by the expression of flagellin (Bosshardt, Benson
& Fields, 1997), although the flagellar protein itself is not a virulence factor (Fields, Benson
& Besser, 2002).
LEGIONELLA AND THE PREVENTION OF LEGIONELLOSIS