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

morphology. ∆PAPI-1∆PAPI-2 leaves the cells susceptible to immune attack and
acts as a trigger to switch to SCV morphology. In this state, the colonies are small
and attached tightly in a biofilm, therefore less mobile and in turn cause a reduction
in dissemination from the lungs to the blood. This explanation could be used to
partially explain, the severely reduced numbers found within the blood and also the
lower numbers found within the lungs, as these SCV colonies are less likely to
reproduce. The cells cannot revert back to normal morphology due to the loss of
PvrR. This could also be used to explain the mice death at 72 hours post-infection,
as SCV colonies persist within the lungs and in the later stages of infection gain an
advantage. It would be interesting further work to analyse cells that have changed to
the SCV phenotype and unable to revert and the subsequent impact on virulence.
He et al. (2004) reported that disrupting genes within PAPI-1 caused a reduction in
mortality compared with wild-type PA14 in a mouse burns-sepsis model. In the
acute respiratory model, the mortality of mice infected with either wild-type PA14
or ∆PAPI-1 was identical. The results generated from the murine intravenous sepsis
model supports He et al. (2004) data. PAO1 and all the PA14 isogenic mutants
infected mice survived till the endpoint of the experiment (24 hours) but PA14
infected mice had to be culled 6 hours post-infection.
In summary, despite the loss of PAPI-1 on its own having no noticeable effect on
virulence, there is a role for PAPI-1 in acute respiratory infection. This is
demonstrated by further reduction of virulence between ∆PAPI-2 and ∆PAPI-
1∆PAPI-2. The discussion in this subsection suggests there is no notable reduction
in virulence due to the potency of ExoU and its importance in respiratory infection.
The masking effects of ExoU have been noted in other models, the true role of the
loss of ExoT could not be seen until ExoU had also been deleted (Cowell et al.
2000). This work therefore can highlight the need for deletion of ExoU to truly
determine the role of any other island or suspected virulence factors. The role of
PAPI-1 is further established with my intravenous model that shows that the loss of
PAPI-1 attenuates the strain allowing the mice to survive 24 hours in comparison to
the 6 hours of the wild-type parent. This could also show that PA14 has adapted to a
role as burns-sepsis clinical strain PA14 was originally isolated from burns patient.
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