46 – I.1. BACTERIA: PATHOGENICITY FACTORS
Jacobs Jr., 2003) is dependent upon their ability to acquire magnesium while inhabiting
the phagosome.
Ability to damage or kill host
To counter infection the human host relies, initially, on the innate immune system.
Prior to mounting an immune response, however, the host must first detect the pathogen.
The innate immune system uses^ sets of recognition molecules, called pattern recognition^
receptors.
The toll-like receptors (TLRs) are one of the most important^ pattern recognition
receptor families (Armant and Fenton, 2002). Pattern recognition^ receptors bind
conserved molecular^ structures, unique to micro-organisms, termed pathogen-associated^
molecular patterns. Pathogen-associated^ molecular patterns such as peptidoglycan,
teichoic acids, LPS, mycolic acid and mannose, bind to pattern recognition^ receptors on a
variety of defense cells of the body causing them to synthesise and secrete a variety of
cytokines. These cytokines can, in turn promote innate immune defenses such as
opsonisation, activation^ of proinflammatory signaling cascades, phagocytosis, activation
of the complement and coagulation cascades, and apoptosis (Wilson et al., 2002).
The host immune response plays a critical role in determining disease manifestations
of chronic infections. Inadequate immune response may fail to control infection, although
in other cases the specific immune response may be the cause of tissue damage and
disease. Not infrequently, host defense mechanisms go overboard and it is this
overaggressive immune response which contributes to the tissue damage observed with
some infections.
A number of bacterial proteins that act as immune modulators are presented in
Table 1.3. This chapter, however, focuses on specific bacterial factors directly responsible
for tissue damage or host death.
Bacteria produce a large number of cell-associated or secreted proteins which play a
role in colonisation, infection and subsequent tissue damage. The great majority of
bacterial virulence factors are secreted products that augment the survival of the bacteria
and/or damage the host (Jett, Huycke and Gilmore, 1994; Fournier and Philpott, 2005;
Kuehn and Kesty, 2005). The following is a summary of activities of many bacterial
proteins that contribute to host invasion, tissue damage or death.
Collagenase
Collagenase, produced by Clostridium histolyticum and Clostridium perfringens
(Legat, Griesbacher and Lembeck, 1994; Rood, 1998), breaks down collagen, the single
most abundant protein in mammals. Collagenases are thought to play a major role in the
pathology of gas gangrene caused by clostridia because they can destroy the connective
tissue barriers.
Spreading factor
Hyaluronidase, or more descriptively “spreading factor”, affects the physical
properties of tissue matrices and intercellular spaces. Hyaluronidase, an enzyme produced
by streptococci, staphylococci and clostridia (Bergan, 1984; Li et al., 2000), is also a
component of venom from snakes, spiders, jellyfish, etc. (Girish et al., 2004;
Kuhn-Nentwig, Schaller and Nentwig, 2004). The enzyme attacks the ground substance
of connective tissue by depolymerising hyaluronic acid thereby promoting the spread of
