5 The role of quorum-sensing in the virulence of Pseudomonas ...

5.3.1 Over-expression of quorum-sensing products as a marker for
virulence in an acute respiratory model
Several LES isolates have been highlighted to exhibit an over-expression of
quorum-sensing products labelled as the hypervirulence phenotype (Fothergill et al.
2007, Salunkhe et al. 2005). An increased virulence of LES isolates with the
hypervirulence phenotype was first noted in a Drosophila fly model of infection
(Salunkhe et al. 2005); when comparing over-expressing quorum-sensing products
isolate LES431 to that of a quorum-sensing deficient isolate LES400. These
findings were later replicated in a C. elegans model of infection (Winstanley C,
University of Liverpool, unpublished), where isolates with the hypervirulence
phenotype (including LESB58 and LESB65) had a lower LT50 in the slow killing
assay.
Previously published work has shown that a deficiency in the quorum-sensing
system can reduce virulence in a number of acute murine infection models. The use
of quorum-sensing deficient mutants in a murine burns injury model led to a
reduction in mortality of the mice and the ability of the bacteria to disseminate
(Rumbaugh et al. 1999). In a murine interperiontal infection model they noted that
clearance of the bacteria was more rapid in quorum-sensing deficient mutants
(Christensen et al. 2007). There have also been two previous studies (Pearson et al.
2000, Tang et al. 1996) that have shown that in a neonatal murine acute respiratory
model the loss of quorum-sensing related genes resulted in a reduction in morbidity
and mortality. The models involved using 7 to 10 day old Balb/c mice inoculating
them with either 5x10 6 CFU (Tang et al. 1996) or 1 x10 9 CFU (Pearson et al. 2000)
per mice. Pearson et al, constructed a PAO1 mutant which lacked two quorum-
sensing associated genes (lasI and rhlI), termed PAO_JP2. Using this mutant in the
neonatal respiratory model increased the survival of the mice (21% versus 5%), as
well reducing the chance of developing pneumonia (56% versus 10%) and
bacteraemia (~50% versus ~15%) 18 hours post-infection when compared with the
wild-type, PAO1. Tang et al, presented similar results using a lasR mutant of
PAO1.
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