50 – I.1. BACTERIA: PATHOGENICITY FACTORS
threshold concentration and the LuxR-autoinducer complexes activate target gene
transcription, including virulence genes (Wagner et al., 2007). Over 50 species of
gram-negative bacteria produce acylated homoserine lactones that differ only in the acyl
side chain moiety, and each LuxR-type protein is highly selective for its cognate
autoinducer signal molecule (Bassler, 2002).
The autoinducers in the QS system of a gram-positive bacterium are short, usually
modified peptides processed from precursors. In contrast with the diffusible behaviour of
AI-1 autoinducers, these signals are actively exported out of the cell (through
an ATP-binding cassette transporter, ABC-transporter), and interact with the external
domains of membrane bound sensor proteins. Signal transduction triggers a
phosphorylation cascade that culminates in the activation of a DNA binding protein that
controls transcription of target genes. Similar to gram-negative bacteria, gram-positive
bacteria can use multiple autoinducers and sensors (Bassler, 2002).
Finally, a third QS pathway, initially discovered in the V. harveyi bioluminescence
system, is mediated by the luxS gene locus (the autoinducer synthase gene) and related
homologues. Signaling elements in this system, termed type 2 autoinducers (AI-2), are
composed of rather complex, unusual, multiple-ringed, cyclical furanosyl-borate diester
molecules. The AI-2 pathway uses a more complex, two-component membrane receptor,
LuxPQ, comprised of periplasmic binding protein (LuxP) and histidine sensor kinase
(LuxQ) subunits (Neiditch et al., 2006). Components of this system are detectable in
almost one-half of all sequenced bacterial genomes, so this system is now recognised as
the most ubiquitous signaling system employed by both gram-negative and gram-positive
bacteria. It has been proposed that the AI-2 pathway is a more universal, interspecies
chemical language (Bassler, 2002).
Quorum sensing molecules and systems show a remarkable array of very complex
properties. These systems are also capable of influencing environmental processes.
Geochemical and biological modifications of signals probably occur in extracellular
environments, and these could disrupt or interfere with intended communication signals.
It has been postulated that quorum sensing occurs within cell clusters, where signal
dispersion might be significantly influenced by existing extracellular polymers (Decho,
Norman and Visscher, 2010).
Molecular aspects of pathogenicity
Molecular genetic definition of bacterial virulence
The application of molecular biology to microbial pathogenesis was described by
Falkow (1988) in a molecular form of Koch’s postulates: 1) the phenotype or property
under investigation should be associated with pathogenic members of a genus or
pathogenic strains of a species; 2) specific inactivation of the gene(s) associated with the
suspected virulence trait should lead to a measurable loss in pathogenicity or virulence;
and 3) reversion or allelic replacement of the mutated gene should lead to restoration of
pathogenicity. Meeting these postulates requires the technical possibility to directly affect
the genes in question, and, even more important, the availability of models to measure
virulence. As this is not always feasible, an alternative approach was added: 4) the
induction of specific antibodies to a defined gene product should neutralise pathogenicity.
This fourth postulate is sometimes taken alone: when antibodies against a certain factor
protect an animal from disease, this is sufficient to call this factor a virulence factor.
