(Keren et al. 2004 ). Clinically, relevant examples of QS in veterinary medicine
have been reviewed elsewhere (Boyen et al. 2009 ).
QS is defined as first the capacity to detect extracellular, small molecule signals
and then to alter gene expression in response to bacterial population densities. QS
signalling is mediated by autoinducers that can be divided into three major classes:
N-acyl homoserine lactones (AHLs) that are produced by over 70 species of Gram-
negative organisms; oligopeptides that are generally produced by Gram-positive
bacteria; and autoinducer-2 (AI-2) which is used by Gram-negative and positive
pathogens and is thought to provide a mechanism for interspecies signalling
(Kaufmann et al. 2008 ).
Elements of the QS apparatus of bacteria serve a variety of functions, including
the coordination of gene expression within a bacterial species and either the
inhibition or the activation of transcriptional programmes among competing bacte-
rial strains and species. In response to these signals, some bacteria appear to exhibit
a form of “altruistic” behaviour, undergoing a programmed cell death, releasing the
sticky DNA that facilitates the formation of the biofilm matrix (Rice and Bayles
2008 ). This bacterial communication system can even alter transcriptional progra-
mmes in eukaryotic epithelial cells and immune effector cells (Asad and
Opal 2008 ).
Staphylococci have QS systems in which the accessory gene regulator (agr) is
genus specific and uses a post-translationally modified peptide as an autoinducing
signal.S. aureusandS. epidermidisagr control the expression of a series of toxins
and virulence factors and the interaction with the innate immune system. Theagr
system is a QS gene cluster that up-regulates production of secreted virulence
factors and down-regulates production of cell-associated virulence factors in a cell
density dependent manner. A second QS system of staphylococci, luxS, is also
found in a range of Gram-positive and Gram-negative bacteria (Kong et al. 2006 ).
Unlike many of the QS systems described in Gram-negative bacteria, agr and luxS
of staphylococci reduce rather than induce biofilm formation and virulence during
biofilm-associated infection. When the staphylococci are in lag phase, it is thought
that staphylococci initiate infection by synthesisng surface proteins. Once colonisa-
tion is established, the bacteria multiply and enter an exponential phase, activating a
density-sensing mechanism that stimulates toxic exoprotein production, thereby
enabling them to spread to new sites to prevent overcrowding. The agr signalling
molecule enhances biofilm detachment by up-regulation of the expression of deter-
gent-like peptides, whereas luxS reduces cell-to-cell adhesion by down-regulating
expression of biofilm exopolysaccharide (Projan and Novick 1997 ; Kong et al.
2006 ). Accordingly, it is not surprising that theagrgene appears to be responsible
for the exponential-phase induction of toxin transcription inStaphylococcus inter-
medius,the most common cause of skin infection in dogs (Sung et al. 2006 ).
There are several examples in nature of mechanisms that inhibit bacterial QS
(Horswill and Nauseef 2008 ):
l Marine algae produce compounds that compete for the AHL signalling mechan-
isms released by Gram-negative organisms.254 M. Martinez and P. Silley