dictyNews
Electronic Edition
Volume 35, number 16
Dec 3, 2010
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Abstracts
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Molecular pharmacology in a simple model system: implicating MAP kinase
and phosphoinositide signalling in bipolar disorder
Marthe H.R. Ludtmann, Katrina Boeckeler and Robin S.B. Williams
Centre for Biomedical Sciences, School of Biological Sciences,
Royal Holloway University of London, Egham TW20 0EX, UK
Seminars in Cell and Developmental Biology, in press
Understanding the mechanisms of drug action has been the primary focus
for pharmacological researchers, traditionally using rodent models. However,
non-sentient model systems are now increasingly being used as an
alternative approach to better understand drug action or targets. One of
these model systems, the social amoeba Dictyostelium, enables the rapid
ablation or over-expression of genes, and the subsequent use of isogenic
cell culture for the analysis of cell signalling pathways in pharmacological
research. The model also supports an increasingly important ethical view
of research, involving the reduction, replacement and refinement of animals
in biomedical research. This review outlines the use of Dictyostelium in
understanding the pharmacological action of two commonly used bipolar
disorder treatments (valproic acid and lithium). Both of these compounds
regulate mitogen activated protein (MAP) kinase and inositol
phospholipid-based signalling by unknown means. Analysis of the molecular
pathways targeted by these drugs in Dictyostelium and translation of
discoveries to animal systems has helped to further understand the
molecular mechanisms of these bipolar disorder treatments.
Submitted by Robin Williams [[log in to unmask]]
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Evolutionary crossroads in developmental biology: Dictyostelium discoideum
Pauline Schaap
College of Life Sciences, University of Dundee, Dundee, UK.
Development, in press
Dictyostelium discoideum belongs to a group of multicellular life forms
that can also exist for long periods as single cells. This ability to shift
between uni- and multicellularity makes the group ideal for studying
the genetic changes that occurred at the crossroad between uni- and
multicellular life. In this Primer, I discuss the mechanisms that control
multicellular development in Dictyostelium discoideum, and reconstruct
how some of these mechanisms evolved from a stress response in the
unicellular ancestor.
Submitted byPauline Schaap [[log in to unmask]]
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Evolution of Pseudomonas aeruginosa virulence revealed in a
Dictyostelium discoideum host model
Emmanuelle Lelong, Anna Marchetti, Marianne Simon, Jane L. Burns,
Christian van Delden, Thilo Köhler, Pierre Cosson*
* Corresponding author: [log in to unmask]
Clinical Microbiology and Infection, in press
Pseudomonas aeruginosa can cause acute lung infections in intubated
patients or chronic infections in patients with cystic fibrosis (CF). In both
situations, P. aeruginosa accumulates specific mutations, in particular
in the lasR quorum-sensing regulator gene. Using a Dictyostelium
discoideum amoeba model, we assessed whether these mutations affect
bacterial virulence.
In a collection of clinical isolates from 16 CF patients, initial isolates were
fully virulent in 15 patients, but in late isolates collected several years later,
virulence was decreased in 8 patients. No significant correlation between
genetic inactivation of lasR and decreased virulence was observed. In
strains isolated from 10 colonized intubated patients, all initial isolates
were fully virulent. Despite the accumulation of lasR-inactivating mutations
in strains collected over a three-week period, no decrease in virulence was
observed in 8/10 patients. In one intubated patient, the virulent initial strain
was replaced a few days later with a different less virulent strain. We
observed a gradual decrease in bacterial virulence in only one intubated
patient.
We conclude that adaptation of P. aeruginosa to chronically infected CF
patients can lead to a slow and gradual loss of virulence, as measured in
a Dictyostelium model system. However, loss of virulence is not caused
predominantly by mutations in lasR. During short-term colonization of
intubated patients up to 20 days, a decrease in virulence was exceptional,
despite the accumulation of lasR mutations.
Submitted by Emanuelle Lelong [[log in to unmask]]
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What does Dictyostelium bring to the study of Pseudomonas infections?
Wanessa C Lima, Emmanuelle Lelong, Pierre Cosson
Corresponding Author: Dr Pierre Cosson
Seminars in Cell and Developmental Biology
Bacterial infections are complex events. They are studied in a variety
of simple model systems, using mammalian or non-mammalian hosts,
all of which fail to reproduce fully the situation in infected patients. Each
model presents a combination of conceptual, practical, and ethical
advantages and disadvantages. In this review, we detail the use of
Dictyostelium discoideum amoebae as a model to study Pseudomonas
aeruginosa. More specifically, our aim is to explore what this additional
model system can bring to our understanding of Pseudomonas infections.
The study of interactions between Dictyostelium amoebae and Pseudomonas
provides a view of the selection pressures exerted by environmental predators
on Pseudomonas. It also represents a unique system to assess the virulence
of very large numbers of Pseudomonas strains.
Submitted by Emanuelle Lelong [[log in to unmask]]
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[End dictyNews, volume 35, number 16]
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