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Legionellosis pneumophila bacterium Developmental factors and their impact (draft)

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All the work in this document has been developed in the context of the simulating life teachingunit. This work will focus on the development of the legionellosis disease, and more particularly onthe development of the bacterium which is the main cause, Legionella Pneumophila.The plan of thiswork is to evaluate in a computerized way and with a standardized methodology the accuracy ofthe current knowledge on the legionella pneumophila bacterium by reproducing experiments alreadyperformed in a controlled environment. The thesis is composed of three parts: the first part isintended to collect the latest knowledge on the l. pneumophila bacterium, as well as to formatthe data. The second part of the thesis corresponds to the setting up of the technical environmentas well as the discussion of the technical solutions implemented. The third part is related to thesimulation of the l. pneumophila bacterium under conditions of experiments already carried out inlaboratory, whose characteristics were recovered and integrated in the simulation creates part two.In chapter 1, I present the current knowledge on the legionella pneumophila bacterium andmore particularly its development in a controlled environment. The simulation framework will be becovered in chapter 2, with a focus on the technical solutions found to face the problems of simulationof biological phenomena.More than 10 experiments have been reproduced, which is important to verify that the programworks correctly. This will allow in the future to implement additional experiments in a biologylaboratory setting but also in the framework of our simulation, which will allow in fine to correlate the obtained data.
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Legionellosis pneumophila bacterium
Developmental factors and their impact
Sacha Duperret
sduperret@u-bordeaux.fr
University of Bordeaux,
Simulating Life research team,
Talence,
France
March 9, 2022
1
Contents
1 Introduction 5
1.1 Background......................................... 5
1.2 Objectives.......................................... 5
1.3 Methods........................................... 5
1.4 Results............................................ 6
1.5 Discussion.......................................... 6
2 Legionellosis 7
2.1 Legionellosisdisease .................................... 7
2.2 Legionellapneumophila .................................. 8
3 Simulating basics 9
3.1 Simulationframework ................................... 9
3.2 Simulationmechanics ................................... 9
List of Figures
1 Legionella pneumophila bacteria (microscopy image) . . . . . . . . . . . . . . . . . . 5
2 slnova.orglogo(MIT) ................................... 6
3 illustration of aspiration compared to inhalation . . . . . . . . . . . . . . . . . . . . 7
4 Distribution of Legionnaires’ disease cases by month, EU/EEA, 2015–2019 . . . . . . 9
2
Abbreviations
USA United States of America
L. pneumophila Legionella Pneumophila
3
Abstract
All the work in this document has been developed in the context of the simulating life teaching
unit. This work will focus on the development of the legionellosis disease, and more particularly on
the development of the bacterium which is the main cause, Legionella Pneumophila.The plan of this
work is to evaluate in a computerized way and with a standardized methodology the accuracy of
the current knowledge on the legionella pneumophila bacterium by reproducing experiments already
performed in a controlled environment. The thesis is composed of three parts: the first part is
intended to collect the latest knowledge on the l. pneumophila bacterium, as well as to format
the data. The second part of the thesis corresponds to the setting up of the technical environment
as well as the discussion of the technical solutions implemented. The third part is related to the
simulation of the l. pneumophila bacterium under conditions of experiments already carried out in
laboratory, whose characteristics were recovered and integrated in the simulation creates part two.
In chapter 1, I present the current knowledge on the legionella pneumophila bacterium and
more particularly its development in a controlled environment. The simulation framework will be be
covered in chapter 2, with a focus on the technical solutions found to face the problems of simulation
of biological phenomena.
More than 10 experiments have been reproduced, which is important to verify that the program
works correctly. This will allow in the future to implement additional experiments in a biology
laboratory setting but also in the framework of our simulation, which will allow in fine to correlate
the obtained data.
Bacteria details Legionella pneumophila is a ubiquitous bacterium, which colonizes artificial
environments, wet soils as well as natural fresh water [1].
Bacteria transmission Bacteria are transmitted to humans by aerosolization and less often by
aspiration (to the lung) of colonized water. For now, relation between infection and water ingestion
(to digestive organs) is not demonstrated.
4
Figure 1: Legionella pneumophila bacteria (microscopy image)
Photo by Janice Haney Carr, Dr. Rodney Donlan, USCDCP
1 Introduction
1.1 Background
This research is conduct in parallel with the Simulating Life course, at the University of Bordeaux,
Talence, France. The study goals is about L. pneumophila growing. Indeed this bacteria has an
ability to cause Legionellosis disease.
1.2 Objectives
The objective is to consolidate the current data on these bacteria by testing them in a mathe-
matical/computer simulation. This study is simulating various factor (for now only including basic
bacteria colony growing in the future the objective is to add characteristics temperature, water
flow, pression, ... with effect on the bacteria1colony.
1.3 Methods
We started by simulating a bacteria colony growing normally and then added some characteristics
with logic blocks which make explicit all the rules for the colony to grow (e.g. the bacteria can only
1Bacteria is plurial of bacterium
5
grow between certain temperature). The intresting thing is that bacteria can develop without all the
specific needs to be filled
1.4 Results
After simulating a lot of randomized situation with the slnova.org c
, we can see a statistical trend
for the colony to grow much more with certain characteristics between limits. What is interesting
is that the scientific data acquired and validated by the community are analyzed in
accordance with and logical for the organism studied in the context of the simulation.
Figure 2: slnova.org logo (MIT)
From StarLogo Nova, it is a project of the MIT Scheller Teacher Education Program
1.5 Discussion
Many research team are currently working on legionella pneumophila bacterium and all the
caracteristics we discuss on this report. The scientific bases and datas used may evolute. For update
you can found the public (Licensed CC BY-NC-SA 4.0) project of this study, fork and update him.
The result of the study can be discussed, indeed there are biases in the simulation programming
that favor bacteria that have certain characteristics.
6
2 Legionellosis
2.1 Legionellosis disease
Clinical description Human legionellosis is a form of bacterial pneumonia of varying severity,
sometimes fatal. Signs and symptoms includes high to moderate fiver, cough, muscle pain, headaches,
shortness of breath. Sometimes digestive disorders sucha as nausea, vomiting and diarrhea, as well
as neurological disorders occur.
The signs of poor prognosis identified concern:
use of assisted ventilation,
advaced age,
kidney disease,
cancer,
immunosuppression,
prolonged delay in administering medication.
The dignostic is confirmed radiologically in front of an acute pneumonia of bacterial origin. The
duration of the incubation of legionellosis (and therefore the period of exposure) varies from 2 to 10
days2.
Bacteria transmission Bacteria3are transmitted to humans by aerosolization and less often by
aspiration (to the lung) of colonized water. For now, relation between infection and water ingestion
(to digestive organ) is not demonstrated.
Figure 3: illustration of aspiration compared to inhalation
From Virginia departement of Health and Centers from Disease Control and Prevention
Pathophysiology The disease is caused by twenty of the 30 species of the identified group of
bacteria (in 1991 [2]), now more than 60 spices have been identifiedTO CITE.
2During this time, the patient can transmit the disease whitout sign of any symptoms
3Bacteria is plurial of bacterium
7
Epidemiology Frequency of legionella pneumophila bacterium for community-acquired pneumo-
nia is 0.5 to 10%4.
2.2 Legionella pneumophila
The legionella pneumophila is the primary humanpathogenic bacterium ([it] represents 80% bac-
teria that cause legionellosis CITE) in this group and the causative agent of Legionnaires’ disease [2]
(other name of Legionellosis disease). This bacteira is thin, aerobic, pleomorphic, flagellated, non-
spore forming and gram-negative bacterium of the genus Legionella.
Bacteria location The bacterium is found naturally in fresh water. It can also contaminate hot
water tanks, cooling towers.
Detection The bacteria can be detected by immunofluorescence techiques. A fluorescent marker
antibody come attach to the bacteria. This is a technique called indirect fluorescent antibody. Other
tests like ELISA and microagglutination tests may be applied.
For clinical use, the appearance of simple diagnostic in urine tests has favored the search for specific
antigens. It helped a lot in cluster discovery. Indeed, if there are much cases of legionellosis, there
must be a source of bacteria somewhere near.
Biophysiology Legionella pneumophilia is a facultative intracellular parasite that can invade and
replicate inside amoebae (a biological organism which has ability to alter its shape by extending and
retracting pseudopods). Legionella pneumophilia bacteria uses these biological as reservoirs. They
provide protection from stress from the environnement (e.g. chlorination of water, temperature).
Proliferation The bacteria has ability to proliferate on the walls of pipes (biofilms). L. pneu-
mophilia can be aerolized throught showers, sprinklers and other fixtures which may leads to to
infection (after prolonged exposure). When aerolized in mist aire, the bacteria can spread too.
Statistics This bacteria is the cause agent for most of the legionellosis disease. In the USA, there
are approximately 3 infections with L. pneumophilia for 100 000 peoples each years. There are a peak
in the summer. In endemic regions (regions where legionellosis disease is more present) about 4%
to 5%. In France, in 2005, the compulsory declaration took into account 1527 cases of legionellosis
representing 2 cases per 100,000 inhabitants5. On the next figure, you can see the distribution of
legionnaires’ disease in Europe.
Synthesis Legionella pneumophila is a bacterium that grows in water systems and is transmitted
via aerosols. It is responsible for most bacterial pneumonia.
4it is a statistic that varies a lot depending on location and population criteria mainly
5Which is similar to USA statistics
8
Figure 4: Distribution of Legionnaires’ disease cases by month, EU/EEA, 2015–2019
Legionnaires’ disease, Annual Epidemiological Report for 2019, European Center for Disease
Prevention and Control
3 Simulating basics
3.1 Simulation framework
For now the simulation may be separated in 4 zones. The screen will be separated to display all
4 situations :
1. Control situation (t´emoin in french),
2. Random characteristics situation,
3. Other random characteristics situation,
4. Another random characteristics situation.
Characteristics will be discussed in a specific section later
3.2 Simulation mechanics
Basics mechanics We don’t simulate single bacteria (this is a ”tactical” choice, if we use a micro-
size = simulate bacteria one by one, we won’t be able to properly stimulate macro-sized things i
think) so we will have colony *
=item. The relation between them will be : for nsize there will be
10nbacteria (n the value of size).
9
Future mechanics goals Make the bacteria capacity randomized (after looking scientific article
for accurate simulation) for ”surviving” extreme situation (e.g. water at 90 degre celcius, frozen
water)
Characteristics For now the characteristic is only by the size of item. For next step, we want to
talk about the need for L. pneumophila in standing water to grow.
Next simulation objective The idea is to simulate different speeds of water flow. Indeed, if
the biological organism is sufficiently adapted to develop in high-flow water, it may be necessary to
modify the sanitary measures of channeling, conservation / treatment of water. This will be a first
mechanic for simulating colony.
Future characteristics goals Other characteristics may be implemented, such as :
Temperature (negative, low, ambient, high),
Brightness/lighting or dark environment,
Minimum colony size to allow for development.
The objective is to have mechanics relied to every of the previous characteristics so the bacteria can
really ”interact” with environment and the 4 (for now) different situation. The little problem for
now is that the camera zoom reset after all refresh of the web page, and also the PC don’t support
more than 150 items size 1 or 2 moving and interacting : do each item may be a comlete colony and
the size is relied (10nbacteria for nsize) to the number of bacteria ?
10
References
[1] S. Jarraud, M. Reyrolle, H. Meugnier, F. Forey, and J. Etienne. egionellose. la Presse M´edicale
ef´erence, 2007.
[2] M Hong Nguyen, Janet E Stout, and Victor L Vu. Legionellosis. Infectious disease clinics of
North America, 5(3):561–584, 1991.
11
ResearchGate has not been able to resolve any citations for this publication.
  • Janet E Hong Nguyen
  • Stout
  • L Victor
  • Vu
M Hong Nguyen, Janet E Stout, and Victor L Vu. Legionellosis. Infectious disease clinics of North America, 5(3):561-584, 1991.