Candida
Morphogenesis in Candida albicans
Figure 1
Candida albicans is a medically
important micro-organism whichmay be cultivated in vitro. On Sabouraud's
medium, a medium whichis commonly used in medical laboratories, the yeast form
is obtained. Thisform is an unicellular one and it reproduces by budding.
Several otherforms may be obtained in different conditions. Pseudomycelium and
myceliumare filamentous forms. Pseudomycelium grows and elongates by budding
whilemycelium grows continuously at its apex. A fourth form is named
chlamydospore.Chlamydospores appear when Candida albicans is cultivated
on a specialmedium such as Rice cream Agar Tween (RAT) at 28°C.
Chlamydosporesusually are produced from pseudomycelium after a delay of 24
hours. Chlamydosporeproduction is used as a test to distinguish Candida
albicans fromother related species.
Morphological
changes may be the result of environmental condition alteration.Figure 1 shows
all the conversions known to date.
Physiology
of chlamydospore production
- Chlamydospores may be obtained in liquid
medium
see
papers 2 and 6
- Chlamydosopores may be obtained in synthetic
liquid medium
see
papers 3 and 10
§
Sowing density is an important control factor
see
papers 2, 6, 7, 11, and 13
§
The question of anaerobiosis is a complicated one:
see
paper 9
Semi-anaerobiosis
is usually considered as a favorable factor in chlamydosporulation. Semi-anaeorobiosis
is obtained by cultivating Candida albicans under a cover-slip. In this
way, chlamydospores are produced near the edge, under the cover-slip. The
conditions I have experimented (liquid medium in thin film) were aerobic ones,
and I obtained very numerous chlamydospores. My observations had to be
elucidated, which I did by testing several sowing densities on RAT. Candida
albicans were cultivated in Petri dishes, a cover-slip (22 x 32 mm) was set
onto the inoculum and chlamydospores were counted after 24 hours of
cultivation. Results of this experiment are shown on figure 2.
Figure 2
Classical description
of chlamydospores under cover-slip near the edge is only true either for 24
hours results or for the most important sowing density after 48 hours of
cultivation: if observations were done after 48 hours of cultivation,
chlamydospores were viewed under the middle part of cover-slip for the two
lighter sowing density. This observation of a frontier (between an area with -
and another without chlamydospores) which moves in a gradient (here an
anaerobiosis gradient) will be interpret later through Catastrophe theory (see
below)
- Light, chloramphenical and antimycin are
inhibitors of chlamydospore production
see
papers 1 , 8 and 16
§
How chlamydospores break out: chlamydospore readiness
see
paper 11
Interpretation
of experimental results by means of Catastrophe theory
Physiological
studies of chlamydosporulation show that:
- All the control parameters are inter-related
- Chlamydosopores appear suddenly in cultures
- The delay in chlamydospore formation is
related to other parameters of cultivation, sowing density or
anaerobiosis for example
So, chlamydospore
production seems to be an "all or nothing" phenomenon, a complicated
one: several parameters control it at the same time; they have to cross a
threshold; this control threshold is a multidimensional one. Morphogenesis
links environmental continuous change with suddenly changes in shape expressed
by Candida albicans. The catastrophe theory proposes a framework to describe
such phenomena.
What is the catastrophe theory
The
fold
It is the simplest
catastrophe; its potential is: Va(x) = x3/3 - ax.
Qualitatively,
this function may have two different shapes:
if a > 0 then
Va(x) has one maximum and one minimum. If the system is governed by the delay
rule, its state variable stays at this minimum on a stable equilibrium for
x = + SQR(a). For x = - SQR(a), the system would
be on instable equilibrium.
if a < 0 then
Va(x) has neither minimum nor maximum. The x value would be equal to -INF.
The value of a = 0
is critical; it corresponds to a threshold value. When (a) decreases, (x)
decreases as slowly as SQR(a) while (a) > 0. When (a) goes through 0, (x)
jumps suddenly to -INF. This sudden jump is called a catastrophe.
The equilibrium
value of (x) may be plotted vs values of (a). 
That curve is called equilibrium manifold. The set of
critical points in the control space is the called bifurcation set. Here, the
control space is one-dimensional, and there is only one critical value, so the
bifurcation set only consist of a = 0.
The
Cusp
This is the second
catastrophe; One state variable is controlled by two parameters. Its potential
is: Va,b(x) = x4/4 - ax - bx2/2.
Figure 3
Control space is
divided into two areas. Over area 1 + 3, there is only one sheet of
equilibrium manifold, here a surface, that is to say that the potential has
only one minimum:
in area 1 and
in area 3.
Over area 2, there are three
sheets of equilibrium manifold, that is to say that the potential has two
minima and one maximum, which corresponds to an instable equilibrium.
Bifurcation set
split control space into area 2 and area 1 + 3. Bifurcation set
is made of two lines and a cusp point in which the two lines meet. The two
lines are folds: locally, the situation is the same as in a fold, by crossing
these lines one minimum merges with the maximum to disappear.
Catastrophe-teacher
"Catastrophe-teacher"
is an HTML document that includes Java applets. It is an introduction to the
catastrophe theory and some applications. The Java applets help you to
experiment and understand cusp and butterfly. This version is still a draft.
Please help us to improve it. Read "Catastrophe-teacher" on line.
Model for travelling wave
see papers 13, 16,
17 and 18
Previous
experiments on RAT medium have shown that under a cover-slip, one can observe a
frontier between two areas: one with and an other without chlamydospores.
Zeeman have proposed a model to explain this travelling wave phenomenon .
First, if you look
at the pictures below (figure 4), you will see the aspect of a piece similar to
a culture surface of Candida albicans on a gradient. The gradient is on the vertical
axe. The same piece is observed at times 0, 100, 200, ..., 800. The variable
which is observed through that time is the point density. These pictures were
obtained by a computer: the density of points , (x), minimizes a potential V(x)
which is the cusp potential. The pictures show the similar phenomenon as
Candida albicans: On the cultures of Candida albicans in a gradient of
anaeobiosis, a frontier appears, moves, deepens and finally stops.
Figure 4
Figure 4 shows
density of points versus time. This image has to be compared with the Fig. 5
below. It shows the frontier movement (for the model) through the gradient.
Figure 5
Zeeman's model is
constructed from the cusp. There are two control parameters:
location on a
gradient (for chlamydosporulation, a gradient of anaerobiosis) and time. Theses
two parameters are continuous: the anaerobiosis degree changes continuously
while the location movesaway from the edge under the cover-slip. Time is a
compound parameter: it represents all the changes during cultivation (substrate
concentration, and so on). In the model, the variable observedhad also to be
thought of as continuous. Here, the observed variable is the morphology of
Candida albicans which, in a first assay, seems discontinuous; but intermediate
shapes between two morphologies of Candida albicans may be observed. For
example, all transitions exist between yeast and pseudomycelium. In the Zeeman
model of travelling wave, the variable minimizes, locally, a potential whose
value is controlled by two parameters. The potential is that of the cusp and
for some places on the gradient, at a critical time, one minimum of potential
disappears; "morphology" jumps from the equilibrium surface of one
sheet(pseudomycelium) to the other one (chlamydospore).
Figure 6
Figure 6 shows the
bifurcation set in the control space and equilibrium surface. The model expects
the frontier appears, moves and deepens, then slows up and stabilises and
finally deepens further. All these predictions were verified on Candida
albicans cultures and chlamydospores production.
Figure 7 (A B and C)
shows what happens when Candida albicans is cultivated into RAT medium inserted
between two glass strips (figure 7 D). Results A, B and C were obtained for the
following sowing density: 105, 106 and 107
yeasts/ml.
Figure 7: !!! area with
chlamydopspores
Other gradients
were studied: travelling wave on pH gradient is shown on figure 8.
Figure 8: ...The frontier
which moves in pH
List of papers
1 - ANDRIEU S. , DUJARDIN L. & LACOSTE L. -
Action de la lumière sur la chlamydosporulation de Candida albicans. Bull.
Soc.Française Mycol. Med. , 1975, 4, 103-106.
2 - DUJARDIN L. & WALBAUM S. - Influence de la
concentration en glucose et de la densité d'ensemencement sur la production
deschlamydospores de Candida albicans; étude quantitative. Bull. Soc. Française
Mycol. Med. , 1977, 6, 39-44.
3 - DUJARDIN L. & WALBAUM S. - Influence des
facteurs nutritifs (glucose, azote, biotine) sur la production des
chlamydosporesde Candida albicans en milieu synthétique. Bull. Soc. Française
Mycol. Med. , 1977, 6, 177-183.
4 - DUJARDIN L. & WALBAUM S. - Influence de la
durée de préculture sur l'indice de chlamydosporulation de Candida
albicans.Bull. Soc. Française Mycol. Med. , 1977, 6, 173-175.
5 - DUJARDIN L. & WALBAUM S. -
N-acétyl-D-glucosamine et chlamydospores de Candida albicans. Bull. Soc.
Française Mycol.Med. , 1978, 7, 25-28.
6 - DUJARDIN L. , WALBAUM S. & BIGUET J. - La
chlamydosporulation de Candida albicans. Influence de la densitéd'ensemencement
et de la concentration de glucose, d'azote, de biotine et de sels minéraux dans
une décoction de crème de riz. Ann.Microbiol. , 1978, 129 B, 183-193.
7 - DUJARDIN L. & WALBAUM S. - Influence de
l'épaisseur du milieu de culture et de la densité d'ensemencement sur la
productiondes chlamydospores de Candida albicans cultivé sur Riz-Agar-Tween.
Bull. Soc. Française Mycol. Med. , 1979, 8, 5-9.
8 - DUJARDIN L. & WALBAUM S. - Inhibition de la
chlamydosporulation de Candida albicans par le chloramphénicol. Bull.
Soc.Française Mycol. Med. , 1979, 8, 135-138.
9 - DUJARDIN L. & WALBAUM S. -
Chlamydosporulation de Candida albicans: avec ou sans lamelle. Bull. Soc.
Française Mycol.Med. , 1980, 9, 31-34.
10 - DUJARDIN L. , WALBAUM S. & BIGUET J. -
Influence de la concentration du glucose et de l'azote sur la morphologie
deCandida albicans et la formation de ses chlamydospores dans un milieu de
culture synthétique. Mycopathologia, 1980, 71, 113-118.
11 - DUJARDIN L. , WALBAUM S. & BIGUET J. -
Chlamydosporulation de Candida albicans: déroulement de la morphogenèse;influence
de la lumière et de la densité d'ensemencement. Ann. Microbiol. , 1980, 131 A,
141-149.
12 - DUJARDIN L. & WALBAUM S. - Variation
quantitative des paramètres externes et morphologie de Candida albicans en
culturecontinue. Bull. Soc. Française Mycol. Med. , 1980, 9, 189-192.
13 - DUJARDIN L. & WALBAUM S. - Vague de
chlamydosporulation de Candida albicans sur différents gradients. Bull.
Soc.Française Mycol. Med. , 1981, 10, 53-56.
14 - WALBAUM S. & DUJARDIN L. - Production de
tubes germinatifs par les jeunes chlamydospores de Candida albicans. Bull.Soc.
Française Mycol. Med. , 1981, 10, 175-178.
15 - DUJARDIN L. & WALBAUM S. - Influence de la
température et du pH sur les phénomènes de blastèse et de chlamydosporulationde
Candida albicans dans un milieu de culture synthétique. Bull. Soc. Française
Mycol. Med. , 1982, 11, 5-8.
16 - DUJARDIN L. - Morphogenèse de Candida albicans,
(Robin) Berkhout: Etude physiologique de la chlamydosporulation
etinterprétation à l'aide de la théorie des catastrophes. Thèse de Doctorat ès
Sciences, Lille, 1982.
17 - DUJARDIN L. & WALBAUM S. - Apport de la
théorie des catastrophes à la description de la morphogenèse de Candida
albicans.Physiologie Végétale, 1985, 23, 309-320.
18 -DUJARDIN L. - Modélisation de la morphogenèse de
Candida albicans par la théorie des catastrophes. in H. LE GUYADER -
Ledéveloppement des végétaux; aspects théoriques et synthétiques. Masson,
Paris, 1987.
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