I.1. BACTERIA: PATHOGENICITY FACTORS – 39
H. influenzae (St. Geme III, de la Morena and Falkow, 1994; St. Geme III, Cutter and
Barenkamp, 1996; Barenkamp and St. Geme III, 1996; Yeo et al., 2004); BabA of
H. pylori (Ilver et al., 1998); UspA2, UspA2h of Moraxella catarhalis (Aebi et al., 1998;
Lafontaine et al., 2000) and rOmpA of Rickettsia spp. (Crocquet-Valdes, Weiss and
Walker, 1994).
The AT secretion system is a modular structure consisting of three domains.
These include a C-terminal transporter or β domain, an internal passenger domain and
an N-terminal signal sequence. The β-domain ends up being inserted as an oligomer in
the OM while the passenger domain is the protein moiety eventually presented on and
anchored to the cell surface (Henderson, Navarro-Garcia and Nataro, 1998; Veiga,
de Lorenzo and Fernandez, 2003; Desvaux, Parham and Henderson, 2004). The AT
secretion system tolerate a wide range of protein modules that become displayed with the
same structure, which favours the emergence of novel adhesins with new specificities.
Veiga, de Lorenzo and Fernandez (2003) have demonstrated this property by creating
hybrid fusion proteins containing the β-AT domain of an AT protein of Neisseria
gonorrhoeae and the partner leucine zippers of eukaryotic transcription factors Fos and
Jun. When the hybrid proteins were expressed in E. coli, the cells acquired novel
adherence traits resulting in the self-association and clumping of planktonic bacteria in
liquid media, or in formation of stable consortia between cells of strains expressing the
dimerisation domains.
Another type of adherence is bacterial attachment to a surface and each other to form
a biofilm. In a biofilm the adherence is mediated by an extracellular polysaccharide slime
that acts as a kind of non-specific (although the signal to produce the biofilm may be
specific) glue to bind the bacteria to each other and to a surface (Watnick and Kolter,
2000; Salyers and Whitt, 2002).
Many microbes can occupy a variety of habitats whereas others are confined to a
specific microenvironment. The range of hosts, tissues or cell types colonised by bacteria
is determined, in part, by adhesin recognition of and affinity for host receptors. For
example, most Bordetella spp. can cause a similar disease in the upper respiratory tract of
many mammals but their host specificities can differ considerably. B. pertussis is human
specific while B. bronchisepta is responsible for infecting a wide variety of mammals and
birds but only rarely causes disease in humans. Strains of B. parapertussis can be divided
into two groups, one which is human specific, the other ovine specific (Cummings et al.,
2004).
Host invasion
Subsequent to attachment, the bacterium may or may not invade the host, depending
upon the pathogen. In any case, the host-associated pathogen must now repel the host
defenses. Infection is the invasion of the host by micro-organisms, which then multiply in
close association with the host’s tissues. Mechanisms that enable a bacterium to invade
eukaryotic cells make entry possible at mucosal surfaces. Whereas some invasive bacteria
are obligate intracellular pathogens, most are facultative intracellular pathogens. In many
cases, the exact bacterial surface factors that mediate invasion are not known, and
multiple gene products are frequently involved. Pathogens may have mechanisms to
disguise or switch antigens on their surface, thus confusing humoral and cellular
immunity. Defensive mechanisms include the expression of proteins and enzymes to
destroy phagocytes and weaken surrounding host tissues, making it easier to spread to