Estudi Epidemiològic I Dels Patrons Antimicrobians Del Bacteri Intracel·Lular Facultatiu Legionella a L’Ambient

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Estudi Epidemiològic I Dels Patrons Antimicrobians Del Bacteri Intracel·Lular Facultatiu Legionella a L’Ambient ADVERTIMENT. Lʼaccés als continguts dʼaquesta tesi queda condicionat a lʼacceptació de les condicions dʼús establertes per la següent llicència Creative Commons: http://cat.creativecommons.org/?page_id=184 ADVERTENCIA. El acceso a los contenidos de esta tesis queda condicionado a la aceptación de las condiciones de uso establecidas por la siguiente licencia Creative Commons: http://es.creativecommons.org/blog/licencias/ WARNING. The access to the contents of this doctoral thesis it is limited to the acceptance of the use conditions set by the following Creative Commons license: https://creativecommons.org/licenses/?lang=en Tesi doctoral / Doctoral thesis: Estudi epidemiològic i dels patrons antimicrobians del bacteri intracel·lular facultatiu Legionella a l’ambient. Environmental epidemiology and antimicrobial surveillance of the facultative intracellular bacteria Legionella. Tíscar Graells Universitat Autònoma de Barcelona Facultat de Biociències Departament de Genètica i de Microbiologia Programa de Doctorat en Microbiologia Bellaterra, 2018 Tesi doctoral / Doctoral thesis: Estudi epidemiològic i dels patrons antimicrobians del bacteri intracel·lular facultatiu Legionella a l’ambient. Environmental epidemiology and antimicrobial surveillance of the facultative intracellular bacteria Legionella in the environment. Autora / Author: Tíscar Graells Directora / Supervisor: Emma Padilla Tutor / Co-supervisor: Jordi Mas Tesis doctoral realitzada al Servei de Microbiologia de Catlab Centre Analítiques AIE i al Departament de Bioquímica mèdica i Microbiologia de la Universitat d’Uppsala, com a estada internacional, amb el vistiplau de la Directora i Tutor: Thesis done in the Microbiology Department at Catlab Centre Analítiques AIE and in the Department of Medical Biochemistry and Microbiology at Uppsala University, as international internship, with the approval of the supervisor and co-supervisor: Tíscar Graells Emma Padilla Jordi Mas Bellaterra, Setembre 2018. Tesis Doctoral presentada per Tiscar Graells per optar al títol de Doctora amb Menció Europea Internacional dins el Programa de Doctorat en Microbiologia per la Universitat Autònoma de Barcelona. Doctoral thesis presented by Tiscar Graells for the Degree of Doctor of Philosophy with International European Mention inside the Microbiology Program at Universitat Autònoma de Barcelona. 2 A la meva família, que sempre m’ha fet costat, encara que moltes vegades sense entendre el que faig. En especial, a la iaia Rosa i a la iaia Magda. 3 4 Índex Índex.............................................................................................................................................. 5 Índex d’imatges ............................................................................................................................ 7 Índex de taules.............................................................................................................................. 9 Abbreviations / Abreviatures: .................................................................................................... 10 Resum // Summary .................................................................................................................... 12 1. Introducció .......................................................................................................................... 14 1.1. El camp de la microbiologia ........................................................................................ 14 1.2. Descobriment de la Legionella .................................................................................... 14 1.3. Actualitat ..................................................................................................................... 16 1.3.1. Epidemiologia ...................................................................................................... 16 2. Legionella ............................................................................................................................ 19 2.1. Descripció general i morfologia .................................................................................. 19 2.2. Taxonomia ................................................................................................................... 20 2.3. Característiques fisiològiques i metabolisme.............................................................. 21 2.4. Genoma ....................................................................................................................... 22 2.5. Ecologia ....................................................................................................................... 24 2.5.1. Amebes ................................................................................................................ 24 2.5.2. Biofilms ................................................................................................................ 27 2.5.3. Temperatura ........................................................................................................ 29 2.5.4. Relació amb altres bacteris ................................................................................. 30 2.5.5. VBNC (Cèl·lules viables però no cultivables) ....................................................... 31 2.5.6. Cicle cel·lular ....................................................................................................... 31 2.5.7. Sistemes de distribució d’aigua artificials ........................................................... 34 2.6. Patogenicitat i factors de virulència ............................................................................ 35 2.6.1. T4BSS ................................................................................................................... 35 2.6.2. Envolta cel·lular ................................................................................................... 35 2.6.3. Pilis i flagel ........................................................................................................... 38 2.7. Manifestacions Clíniques ............................................................................................ 39 2.7.1. Mecanismes de transmissió ................................................................................ 39 2.7.2. Formes clíniques i factors de risc: ....................................................................... 40 2.7.3. Diagnòstic ............................................................................................................ 41 2.7.4. Sensibilitat antibiòtica natural ............................................................................ 43 5 2.7.5. Tractament .......................................................................................................... 44 2.7.6. Tipificació molecular ........................................................................................... 45 2.8. Prevenció ..................................................................................................................... 47 2.8.1. Control d’instal·lacions ........................................................................................ 51 2.8.2. Bases microbiològiques de la resistència de Legionella als mètodes de desinfecció........................................................................................................................... 52 2.8.3. Estudi de brots .................................................................................................... 53 2.9. Immunitat .................................................................................................................... 54 2.10. Estudis metagenòmics ............................................................................................. 56 3. Justificació de la tesi ........................................................................................................... 57 4. Objectius ............................................................................................................................. 58 4.1. Objectius específics article I: Legionella pneumophila recurrently isolated in a Spanish hospital: Two years of antimicrobial resistance surveillance ................................................. 58 4.2. Objectius específics article II: The all-intracellular order Legionellales is unexpectedly diverse, globally distributed and lowly abundant ................................................................... 59 5. Resultats ............................................................................................................................. 60 5.1. Article I: Legionella pneumophila recurrently isolated in a Spanish hospital: Two years of antimicrobial resistance surveillance .................................................................................. 60 5.2. Article II: The all-intracellular order Legionellales is unexpectedly diverse, globally distributed and lowly abundant .............................................................................................. 61 6. Discussió general ................................................................................................................ 62 7. Conclusions ......................................................................................................................... 69 7.1. Conclusions article I: Legionella pneumophila recurrently isolated in a Spanish hospital: Two years of antimicrobial resistance surveillance ................................................. 69 7.2. Conclusions article II: The all-intracellular
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