Elucidating Metabolic and Drug Resistance Adaptations of Morganella Morganii with Possible Links to Virulence
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Texas A&M International University Research Information Online Theses and Dissertations 6-15-2021 Elucidating Metabolic and Drug Resistance Adaptations of Morganella morganii with Possible Links to Virulence Yuridia Rodriguez Follow this and additional works at: https://rio.tamiu.edu/etds Recommended Citation Rodriguez, Yuridia, "Elucidating Metabolic and Drug Resistance Adaptations of Morganella morganii with Possible Links to Virulence" (2021). Theses and Dissertations. 139. https://rio.tamiu.edu/etds/139 This Thesis is brought to you for free and open access by Research Information Online. It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of Research Information Online. For more information, please contact [email protected], [email protected], [email protected], [email protected]. ELUCIDATING METABOLIC AND DRUG RESISTANCE ADAPTATIONS OF MORGANELLA MORGANII WITH POSSIBLE LINKS TO VIRULENCE A Thesis by YURIDIA RODRIGUEZ Submitted to Texas A&M International University in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE August 2019 Major Subject: Biology ELUCIDATING METABOLIC AND DRUG RESISTANCE ADAPTATIONS OF MORGANELLA MORGANII WITH POSSIBLE LINKS TO VIRULENCE A Thesis by YURIDIA RODRIGUEZ Submitted to Texas A&M International University in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE Approved as to style and content by: Chair of Committee, Daniel J. Mott Committee Members, Keith Combrink C. Neal McReynolds Sebastian Schmidl Head of Department, Michael R. Kidd August 2019 Major Subject: Biology iii ABSTRACT Elucidating Metabolic and Drug Resistance Adaptations of Morganella morganii with Possible Links to Virulence (August 2019) Yuridia Rodriguez, B.S., Texas A&M International University Chair of Committee: Dr. Daniel J. Mott The human gut microbiome has recently gained more attention due to its possible links to metabolic disorders such as obesity, autoimmune disorders, gastrointestinal disorders, and stress-related disorders such as depression and anxiety. In addition, the gut microbiome is often a cause of nosocomial infections due to the fact that they can be opportunistic pathogens. Therefore, many studies are now focusing on the bacteria that belong to the human gut microbiota. One such bacterium is named Morganella morganii. M. morganii is a gram-negative rod shaped bacterium that belongs to the Enterobacteriaceae family. It is a highly adaptive species of bacteria that has clinically been shown to cause infections ranging from septic arthritis to brain abscesses to the most common type being urinary tract infections. However, most studies focus on the clinical aspect of this organism. Therefore, although we have a broad picture at the types of infections that this organism causes, we do not know how it is able to become pathogenic. In order to begin understanding M. morganii’s pathogenicity, it is vital that we begin to study this organism at the molecular level. Therefore, this study will focus on creating a basic metabolic and drug resistance profile for an organism that is relatively unknown at the molecular level. iv ACKNOWLEDGEMENTS I would like to start off by thanking all of the members of my committee, Keith D. Combrink, Michael R. Kidd, C. Neal McReynolds, and Sebastian Schmidl, for their guidance throughout my entire research project. In addition, I would like to thank Daniel J. Mott for being my committee chair and for being my mentor. I would also like to say thank you to the College of Arts & Sciences (COAS) and the Graduate School (GS), for reviewing this thesis. I would also like to recognize the efforts of the undergraduate students who helped me with my research project, including Alejandro Parra, Erendira Perez, Maritza Lozano, Jose Longoria, Lizeth Haro, Lyanna Guerra, Andy Escalante, Ari Montemayor, Fernando Garcia, Stephany Cavazos, Melissa Marchan, Ricardo Martinez, Jannette Tijerina, Hannah Torres, Steven Martinez, Juan Onofre Renteria, Kassandra Lopez, and Orlando Berumen. In addition, I would like to thank my colleagues Bryant De Jesus, Maria Hinojosa, Travis Salinas, and Rafael Deliz Aguirre for their support and guidance throughout my research project. Lastly, I would like to thank my family and friends for all of their encouragement and support. v TABLE OF CONTENTS Page ABSTRACT ............................................................................................................................. iii ACKNOWLEDGEMENTS ..................................................................................................... iv TABLE OF CONTENTS .......................................................................................................... v LIST OF FIGURES ................................................................................................................ vii LIST OF TABLES ................................................................................................................... ix INTRODUCTION .................................................................................................................... 1 History of Microbes ................................................................................................ 1 Microbiota Overview .............................................................................................. 2 Inside the human gut ............................................................................................... 2 Human gut microbiota overview ............................................................................ 4 The role of carbon metabolism in virulence ........................................................... 6 M. morganii characteristics ..................................................................................... 8 M. morganii partnerships ........................................................................................ 9 M. morganii and Urinary Tract Infections .............................................................. 9 M. morganii drug resistance ................................................................................. 10 METHODS ............................................................................................................................. 12 M. morganii culturing ........................................................................................... 12 Preparation of carbon sources ............................................................................... 12 Growth experiments .............................................................................................. 12 Heat map experiments ........................................................................................... 13 Protein expression profiles .................................................................................... 14 Bioinformatics analysis of M. morganii genes ..................................................... 14 Bioinformatic construction of metabolic pathways .............................................. 15 Disk diffusion assays ............................................................................................ 15 Statistical analysis ................................................................................................. 16 RESULTS ............................................................................................................................... 17 Growth curves ....................................................................................................... 17 Statistical analysis ................................................................................................. 31 Heat map experiments ........................................................................................... 36 Protein expression profiles .................................................................................... 43 vi Metabolic pathways ............................................................................................. 50 Disk diffusion assays ........................................................................................... 70 DISCUSSION ......................................................................................................................... 71 REFERENCES ....................................................................................................................... 75 VITA ....................................................................................................................................... 81 vii LIST OF FIGURES Figure 1. Close up look at epithelial lining in human gut ......................................................... 3 Figure 2. Hexose sugars. ......................................................................................................... 17 Figure 3. Pentose sugars . ....................................................................................................... 18 Figure 4. Alcohol sugars. ........................................................................................................ 19 Figure 5. Sugar acids ............................................................................................................... 20 Figure 6. Amino sugars. .......................................................................................................... 21 Figure 7. SCFAs. .................................................................................................................... 22 Figure 8. Nucleoside