I.1. BACTERIA: PATHOGENICITY FACTORS – 43
Phagocytosis comprises several steps:- Recognition and attachment of bacteria to professional (macrophages/neutrophils)
or non-professional phagocytes (e.g. epithelial cells). The recognition is usually
receptor-mediated (e.g. opsonisation – Fc receptors) but can be non-specific (bulk
fluid pinocytosis). - Endocytic entry of bacteria into the phagocytic cell with the generation of a
phagocytic vacuole (endosome, phagosome). - Generation of a phagolysosome via fusion of the phagosome with primary and
secondary lysosomal granules. - Degranulation and killing through the release of lysosomal or granular contents in
direct apposition to the bacteria within the phagolysosome (maybe via
oxygen-dependent and/or oxygen-independent mechanisms of killing).
The various strategies employed by bacteria to avoid destruction by phagocytes
include: 1) adaptation to withstand the antimicrobial activity of the fused phagolysosome;
- alteration of phagocytosis to target the bacterium to a novel phagosome; 3) escape
from the phagosome into the cytosol by lysing the vacuolar membrane; 4) blocking
lysosome/phagosome fusion or attenuating the acidification of phagolysosomes; - circumventing or resisting phagocytosis.
Adaptation to withstand the antimicrobial activity
With some intracellular bacteria, phagosome-lysosome fusion occurs, but the bacteria
are resistant to inhibition and killing by the lysosomal constituents. Also, some
extracellular pathogens can resist killing in phagocytes utilising similar resistance
mechanisms. Resistance to phagocytic killing within the phagocytic vacuole is not
completely understood, but it may be due to the surface components of the bacteria or due
to extracellular substances produced which interfere with the mechanisms of phagocytic
killing. Brucella abortus and Staphylococcus aureus are vigorous catalase and superoxide
dismutase producers, which might neutralise the toxic oxygen radicals that are generated
by the NADPH-oxidase and myeloperoxidase systems in phagocytes. S. aureus also
produces cell-bound pigments (carotenoids) that “quench” singlet oxygen produced in the
phagocytic vacuole. There are some micro-organsims, however, that are dependent upon
phagosome-lysosome fusion for intracellular replication and persistence.
The pH that develops in the phagosome after engulfment induces bacterial gene
products that are essential for their survival in macrophages. For instance, replication and
synthesis of metabolic factors required for intracellular persistence of Coxiella burnetti,
Brucella suis and S. typhimurium is induced by the acidic pH found within the
phagolysosome (Hackstadt and Williams, 1981; Rathman, Sjaastad and Falkow, 1996;
Porte, Liautard and Kohler, 1999; Ghigo et al., 2002).
Alteration of phagocytosis
Bacteria such as Salmonella spp. are able to induce phagocytosis in non-professional
phagocytes. The Salmonella-containing vacuole (SCV), a unique cytoplasmic organelle
formed following phagocytic induction, actually protects the bacterium; Salmonella spp.
interfere with the ability of this phagosome to fully mature into a phagolysosome (Duclos
and Desjardins, 2000).