44 – I.1. BACTERIA: PATHOGENICITY FACTORS
Escape from the phagosome
Escape from the phagosome is a strategy employed by the Rickettsiae. Rickettsia spp.
enter host cells in membrane-bound vacuoles (phagosomes) but are free in the cytoplasm
a short time later, perhaps in as little as 30 seconds. A bacterial enzyme, phospholipase A,
may be responsible for dissolution of the phagosome membrane. Listeria monocytogenes
rely on several molecules for early lysis of the phagosome to ensure their release into the
cytoplasm. These include listeriolysin O (LLO), a cholesterol-dependent cytolysin and
two forms of phospholipase C. The low optimal pH activity of LLO allows the bacterium
to escape from the phagosome into the host cytosol without damaging the plasma
membrane of the infected cell.
Glomski et al. (2002) demonstrated that a single amino acid change from leucine 461
to threonine profoundly increased the hemolytic activity of LLO at a neutral pH and
promoted premature permeabilisation of the infected cells. This discovery demonstrates
how minor changes in proteins can be used by bacterial pathogens to establish and
maintain the integrity of their specific niches or be exploited by researchers working with
bacteria to produce a protein with novel properties. Once in the cytoplasm, Listeria spp.
induce their own movement through a process of host cell actin polymerisation and
formation of microfilaments within a comet-like tail. Shigella spp. also lyse the
phagosomal vacuole and induce cytoskeletal actin polymerisation for the purpose of
intracellular movement and cell-cell spread.
Blocking fusion or attenuating acidification
Some bacteria survive inside of phagosomes by blocking the fusion of phagocytic
lysosomes (granules) with the phagosome thus preventing the discharge of lysosomal
contents into the phagosome environment. This strategy is employed by Salmonella spp.,
M. tuberculosis, Legionella spp. and the chlamydiae. With Legionella spp., it is known
that a single gene is responsible for the inhibition of phagolysosomal fusion. Attenuating
the acidification of phagolysosomes is observed with Rhodococcus spp. Toyooka, Takai
and Kirikae (2005) demonstrated that phagolysosomes did not acidify when they
contained virulent R. equi organisms. Their research indicated that R. equi in
phagolysosomes produced substance(s) to suppress acidification. Results by
Tsukano et al. (1999) indicated that inhibition of phagosomal acidification by
Y. pseudotuberculosis was due to attenuation of vacuolar-ATPase activity.
Phagocytic circumvention
Bacteria may avoid phagocytosis by simply penetrating areas inaccessible to
phagocytes such as the lumens of glands and the urinary bladder and surface tissues such
as the skin.
Other strategies for phagocyte evasion include suppression of the inflammatory
response and inhibition of phagocyte chemotaxis. For example, pneumolysin
(streptolysin) toxin produced by Streptococcus pneumoniae (Paton and Ferrante, 1983;
Ernst, 2000) and components of Mycobacterium spp. inhibit polymorphonuclear
leukocyte (PMN) migration. Also, studies involving pathogen-induced PMN alterations
have suggested that Anaplasma phagocytophilum delays PMN apoptosis and lessens
proinflammatory cytokine release (Yoshiie et al., 2000; Klein et al., 2000). Bacteria using
host cell mimicry for phagocytic evasion cover their surface with a component which is
recognised as “self” by the host phagocytes and immune system. This effectively hides
the antigenic surface of the bacterial cell. Phagocytes are unable to recognise bacteria
