Download Effects of Outer Membrane Vesicles on the Bacterial Phage Defense... Graduate Category: Health/Sustainability Degree Level: M. Sc.

Graduate
Category: Health/Sustainability
Degree Level: M. Sc.
Abstract ID# 1371
M. Sc. Candidate: Masoud Mahdisoltani
Advisor: Ferdi L. Hellweger
Effects of Outer Membrane Vesicles on the Bacterial Phage Defense System
Abstract
𝑟 =𝜑 𝐶−𝑟 −𝜙 𝑛+𝑚
𝜙
𝑛=𝑛
− 𝜑𝑛 − 𝛾𝑛𝑝
𝑒(1 + 𝑓𝑔)
𝜙
𝑣=𝑛
𝑔 − 𝜑𝑣 − 𝛿𝑣𝑝
𝑒(1 + 𝑓𝑔)
Model Description
• Employing theoretical models to simulate the system of bacteria-bacteriophage [3]
• Investigating efficiency of producing OMVs as an innate defense mechanism
• Comparing average limiting resources (R*) for both bacteria with and without OMVs
𝑚 = 𝛾𝑛𝑝 − 𝜑𝑚 − 𝛾𝑛′ 𝑡−𝑙 𝑝′ 𝑡−𝑙 𝑒 −𝜑𝑙
𝑝 = 𝑏𝛾𝑛′ 𝑡−𝑙 𝑝′ 𝑡−𝑙 𝑒 −𝜑𝑙 − 𝜑𝑝 − 𝛾𝑛𝑝 − 𝛿𝑣𝑝
(b)
1E+8
1E+6
1E+4
Resource
Virus
Bacteria
1E+2
1E+0
0
50
100
150
200
250
Concentration (cell/ml or µg/ml)
Figure 3 shows a steady
oscillation among the
populations for both
bacterium with and
without vesicles. It
illustrates a chemostat
model simulation to
fitness
effect
of
producing vesicles.
(a)
Concentration (cell/ml or µg/ml)
Biologists have broadly studied the interaction between bacterium and bacteriophages
,viruses, experimentally and numerically. More recently, it has been discovered that
gram-negative bacterium (e.g. cyanobacteria and heterotroph) release extracellular
vesicles to their habitat. These vesicles are released from the outer membrane of the
bacteria and therefore are called Outer Membrane Vesicles (OMVs).
The reason behind producing bacterial OMVs, which demands resource consumption, is
yet unknown. Since OMVs have the same outer structure as bacteria, it is probable that
they alleviate the viral infection and contribute to the bacterial defense mechanisms. The
question is whether resource consumption for producing vesicles to reduce viral infection
rate is beneficial for the bacteria or not. Mathematical models are employed and some
modifications are applied to them in order to take the presence of OMVs within the habitat
into account. Limited nutrients is the main factor which determines and controls whether
OMVs are effective to decrease the infection by viruses or not. To quantify the efficiency of
OMVs, average limiting resource (R*) is used as an indicator. Lower R* of bacterium with
OMVs in comparison to that of the ones without OMVs demonstrates the usefulness of
vesicles.
In this study, we explore that producing and releasing OMVs under certain conditions can
be beneficial for the bacteria. The major parameters controlling effectiveness of OMVs are
number of released vesicles, relative size of OMV to that of bacteria, viral attack rate, flow
rate through the habitat, and resource inflow. Generally, when the resource concentration
is high and flow rate is low, OMVs are more likely to be considered beneficial for the
bacterium population.
1E+8
1E+6
1E+4
Resource
Bacteria
OMV
1E+2
Virus
Inf. Bacteria
Inf. OMV
1E+0
0
50
100
150
200
250
Time (hr)
Time (hr)
Figure 3. A stable oscillation among populations and concentration of resource
(a) Bacteria does not produce vesicles. (b) Bacteria does produce vesicles.
Result
•
•
•
•
Producing vesicles can be whether beneficial or not under different conditions
Over increasing the number of vesicles per generation will make them inefficient for the bacterium population
Increasing the number of vesicles per generation will eventually make them inefficient for the bacterium population
Relative size of vesicles to the size of bacteria and wash-out rate are major parameters which affect the efficiency of OMVs
1.2
•
•
•
•
Viral Infection affect bacterium population and growth process
Viruses attack the outer-membrane of bacteria
Bacteria responses to infection with Innate defense mechanisms
OMVs are continuously released from outer-membrane as a defense mechanism
Figure 1[1] illustrates how OMVs are
produced and pinched off from
outer-membrane of bacteria. It can
be seen that the OMVs has the same
outer structure as the bacteria;
therefore, viruses attach to them.
Attached viruses to the OMVs cannot
reproduce themselves and eventually
die. Manning AJ and Kuehn MJ
considered “a role for OMVs in
contributing to innate bacterial
defense
by
adsorption
of
bacteriophage.” [2] This method is
similar to countermeasure action to
distract missiles as shown in Figure 2.
OMVs are not beneficential
R* ratio
Introduction
Figure 4 illustrates how
efficiency of producing
vesicles varies as a function
of the number of OMVs
produced per generation.
Each line corresponds to a
different parameter.
Parameters at avg
Wash-out at min
Wash-out at max
Size of OMV at min
Size of OMV at max
Resource Conc. at min
Resource Conc. at max
Inf. rate for OMV at min
Inf. rate for OMV at max
1
OMVs are beneficential
0.8
0
10
20
30
40
50
60
70
80
90
100
#OMV
Figure 4. Fitness effect of producing OMVs as a function of the number OMVs produced per generation for different parameters
Figure 1. Formation of OMVs in gram-negative bacteria
Conclusion
Production of OMVs and releasing them can benefit bacteria depending on a variety of parameters. Mainly, when the viral infection is
responsible for majority of bacterium population loss, OMVs tend to play a crucial role as an innate defense mechanism for bacteria.
Wash-out and relative size of OMV to the one of bacteria appeared to considerably affect efficiency of producing vesicles.
Future Work
For further studies, other biological models can be used to simulate the interaction between bacteria and virus and studying effects of
OMVs on that. It is also recommended to employ experimental methods to validate these findings.
Figure 2. Countermeasure action to prevent a missile attack
Reference
[1] Roier, S., et al. (2016). "A novel mechanism for the biogenesis of outer membrane vesicles in Gram-negative bacteria."
[2] Manning, A., Kuehn, M. (2011). “Contribution of bacterial outer membrane vesicles to innate bacterial defense.”
[3] Levin,B., et al. (1977). “Resource-Limited growth, competition, and predation: A model and experimental studies with bacteria and
bacteriophage.”