I.1. BACTERIA: PATHOGENICITY FACTORS – 55
Examples are the release of nutrients by cell damage, or enabling contagion of the next
host by inducing coughing or diarrhea. The degree of damage is dependent on the
equilibrium that results from the interplay of pathogen and host, and may, for instance, be
dependent on the immune response of the individual (Casadevall and Pirofski, 1999).
Conditions that result in disease can vary among host individuals, and from host species
to host species. This adds to the difficulties to identify the bacterial genes that are directly
responsible for the disease. Ideally, experimental shortcomings, subjective observations
and the anthropomorphic view on pathogenicity should all be considered when
establishing the relevance of a certain virulence gene to the pathogenicity of a micro-
organism.
Classification of virulence genes
From the previous sections it is clear that there are many ways of defining, identifying
and testing virulence genes. But, since each pathogen has evolved to fit its own niche,
different pathogens do not necessarily share common pathogenic characteristics. Despite
the recognition of common themes in bacterial virulence (Finlay and Falkow, 1989;
1997), a larger part of all virulence genes described in the literature that resulted from
over 30 years of research have little in common, other than having some function in
virulence. In order to interpret the vast amount of data on this subject these genes need to
be classified.
As already stated in the introduction to this chapter, regulators dealing with
risk/safety assessment of genetically engineered bacteria need a good understanding of
the significance of a given virulence gene in its physiological background; only if the
newly acquired gene can have a role in the pathogenic lifestyle of the recipient micro-
organism can an interaction be expected between the newly acquired gene and the
resident genes contributing to the pathogenic lifestyle. Wassenaar and Gaastra (2001)
have proposed a classification of virulence genes according to their potential role in
pathogenic lifestyles that should be helpful to evaluate the potential influence of newly
acquired genes on virulence.
Wassenaar and Gaastra (2001) discriminate among four lifestyles: exclusive
pathogens, host-dependent pathogens, opportunistic pathogens and fully non-pathogenic
organisms. Seven types of virulence gene classes are distinguished: true virulence genes,
directly involved in interactions with the host and responsible for pathological damage
(e.g. toxins); colonisation genes, determining the localisation of the infection; host
defense system evasion genes (e.g. immunoglobulin specific proteases); processing genes
involved in the biosynthesis of virulence lifestyle factors (e.g. chaperonins; gene products
with a virulence lifestyle substrate), secretory genes, virulence housekeeping genes
(e.g. urease, catalase) and regulatory genes, involved in the regulation of virulence
lifestyle genes. Further subclasses may be identified for these classes.
Evolution and spread of virulence genes: Pathogenicity islands
In general, three mechanisms can be proposed for the evolution of pathogens:
acquisition of virulence genes from existing pathogens by horizontal gene transfer;
a change in host specificity (host jump) of an existing pathogen, possibly together with,
or as a result of, the acquirement of genes to adapt to a new ecological niche; and
evolution of new virulence genes from the existing gene pool of a bacterial species,
resulting in (an increase of) virulence.