60 – I.1. BACTERIA: PATHOGENICITY FACTORS
constellation of traits in the recipient micro-organism. This may arise as the result, for
example, of the product of an inserted gene acting alongside existing pathogenic
determinants or the addition of a trait completing the suite of traits necessary for a
pathogenic lifestyle. Alternatively it is possible that modification of normal genes may
also alter pathogenicity. In an assessment for environmental risk/safety of an application
intended for environmental release, the following points should be considered:
- characteristics of the recipient, for instance whether the recipient possesses a
sufficient number of the constellation of traits that it could be a potential human
or mammalian pathogen
- existing traits in the recipient organism that might lead to an increase in
pathogenicity or infectivity when altered (e.g. alteration of host range or tissue
tropism)
- the likelihood that any disabling mutation within the recipient might be overcome,
for example through complementation or reversion, due to the insertion of the
foreign DNA, or through the inserted gene encoding an enzyme that would
complete an anabolic pathway for a pathogenicity determinant
- the transmissibility of the vector used to introduce relevant genes
- whether the foreign DNA carries a pathogenicity determinant from a related
organism (toxin, invasin, integrin, and surface structures such as fimbriae, LPS
and capsule)
- when the foreign DNA does carry a virulence factor, the feasibility that this gene
could contribute to the pathogenicity of the genetically engineered micro-
organism, or whether the virulence factor provides resistance to host defense
mechanisms
- whether the foreign DNA carries a gene that renders the recipient resistant to an
antibiotic, especially if the specific resistance has not yet spread by natural
processes to the genus to which the recipient belongs (see Appelbaum, 2006;
Noble, Virani and Cree, 1992), or if the mechanism of resistance has emerged
newly, like Qnr determinants (Nordmann and Poirel, 2005)
- whether susceptibility to antibiotics or other forms of therapy may be affected as a
consequence of the genetic engineering
- whether attenuated or inactivated strains remain stably attenuated or inactivated
- whether a surface component that might bind to a different receptor than that used
by recipient micro-organism could increase virulence
- whether the foreign DNA encodes gene products, e.g. toxins, that even in the
absence of live organisms, may cause pathogenic effects
- whether the derived from unrelated bacteria foreign DNA encodes a protein that
does not interact with the pathogenic properties of the parental strain but may
cause pathogenic reaction, e.g. a modulator of growth (hormone, cytokine), or
other protein with a potentially harmful biological activity (see also
Bergmans et al., 2008)
- when mutations are introduced that inactivate specific virulence factors of
potential pathogens, whether the stability of the mutation has been demonstrated,
