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STUDIES of NEISSERIA MUSCULI TYPE IV PILUS and CAPSULE USING the NATURAL MOUSE MODEL of COLONIZATION and PERSISTENCE by Man Cheo

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STUDIES of NEISSERIA MUSCULI TYPE IV PILUS and CAPSULE USING the NATURAL MOUSE MODEL of COLONIZATION and PERSISTENCE by Man Cheo Studies of Neisseria musculi Type IV Pilus and Capsule Using the Natural Mouse Model of Colonization and Persistence Item Type text; Electronic Dissertation Authors Ma, Man Cheong Publisher The University of Arizona. Rights Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction, presentation (such as public display or performance) of protected items is prohibited except with permission of the author. Download date 27/09/2021 11:29:10 Link to Item http://hdl.handle.net/10150/634345 STUDIES OF NEISSERIA MUSCULI TYPE IV PILUS AND CAPSULE USING THE NATURAL MOUSE MODEL OF COLONIZATION AND PERSISTENCE by Man Cheong Ma Copyright © Man Cheong Ma 2019 A Dissertation Submitted to the Faculty of the DEPARTMENT OF IMMUNOBIOLOGY In Partial Fulfillment of the Requirements For the Degree of DOCTOR OF PHILOSOPHY In the Graduate College THE UNIVERSITY OF ARIZONA 2019 2 3 Table of Contents List of Figures ................................................................................................................................6 List of Tables ..................................................................................................................................7 Abstract ...........................................................................................................................................8 Chapter 1- Introduction ...................................................................................................................... 10 Chapter 1.1 ............................................................................................................................................. 11 Concepts of microbe-host interactions ............................................................................................ 11 Microbial pathogenesis .......................................................................................................... 11 Mutualism, Commensalism, and Parasitism ......................................................................... 13 Chapter 1.2 ............................................................................................................................................. 15 Effects of microbiota on human physiology and gut and immune system development .......... 15 The gastrointestinal tract microbiota ..................................................................................... 16 The upper respiratory tract microbiota .................................................................................. 19 The vaginal microbiota .......................................................................................................... 20 The male genital tract microbiota .......................................................................................... 21 The gut microbiota is essential for maintaining gut physiology ............................................ 22 The gut microbiota directs the development of the gut and systemic immune system ....... 23 The microbiota protects against pathogen colonization ....................................................... 24 Disturbances in the microbiota lead to outgrowth of pathogens and increase the risk of non- infectious diseases ................................................................................................................ 29 Chapter 1.3. ............................................................................................................................................ 31 The genus Neisseria .......................................................................................................................... 31 Human Commensal Neisseria .............................................................................................. 32 Animal commensal Neisseria ................................................................................................ 35 Human pathogenic Neisseria ................................................................................................ 36 Neisseria meningitidis and Neisseria gonorrhoeae .............................................................. 36 Pathogenesis of Neisseria gonorrhoeae and Neisseria meningitidis on mucosal epithelial surfaces ................................................................................................................................. 38 Host interaction factors common to human/animal commensal and pathogenic Neisseria 42 The damage response curve of Neisseria spp. .................................................................... 44 Chapter 1.4 ............................................................................................................................................. 46 Neisserial Tfp and capsule and their cognate host components ................................................. 46 The Neisseria Type IV pilus .................................................................................................. 46 The PilT motor ....................................................................................................................... 48 The Neisseria Polysaccharide Capsule ................................................................................ 50 4 Capsular genes organization and regulation ........................................................................ 51 Chapter 1.5. ............................................................................................................................................ 56 Models for studying Neisseria-host interactions ............................................................................ 56 Models of gonococcal infection ............................................................................................. 56 Models of meningococcal infection ....................................................................................... 58 Developing a natural animal model for studying Neisseria asymptomatic colonization ...... 60 Chapter 2 - Manuscript 1 .................................................................................................................... 63 A mouse model for Neisseria colonization.......................................................................................... 63 Abstract ............................................................................................................................................... 64 Introduction ......................................................................................................................................... 65 Results ................................................................................................................................................. 67 N. musculi colonizes the oral cavity and gut of mice in a mouse strain specific manner. ... 67 N. musculi colonizes the entire gastrointestinal tract of mice. .............................................. 70 Innate immunity determines susceptibility to N. musculi colonization. ................................. 71 N. musculi colonization requires the Type IV pilus. .............................................................. 72 N. musculi encodes host interaction factors and vaccine candidates of human-dwelling Neisseria. ............................................................................................................................... 75 N. musculi expresses a polysaccharide capsule. ................................................................. 78 Discussion ........................................................................................................................................... 80 Supplemental Figures and Tables ................................................................................................... 83 Materials and Methods ...................................................................................................................... 86 Acknowledgments .............................................................................................................................. 93 Chapter 3 ................................................................................................................................................ 94 Type IV Pilus retraction is required for colonization and persistence of commensal Neisseria in vivo ........................................................................................................................................................... 94 Abstract ............................................................................................................................................... 95 Introduction ......................................................................................................................................... 96 Results ................................................................................................................................................. 98 N. musculi DNA uptake requires Tfp retraction. ................................................................... 98 N. musculi colonization requires Tfp retraction. .................................................................... 99 Discussion ......................................................................................................................................... 103 Materials and Methods .................................................................................................................... 106
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