{"662195":{"#nid":"662195","#data":{"type":"event","title":"PhD Defense by Madeline Mei","body":[{"value":"\u003Cp\u003EIn partial fulfillment of the requirements for the degree of\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EDoctor of Philosophy in Biology\u003C\/p\u003E\r\n\r\n\u003Cp\u003EIn the\u003C\/p\u003E\r\n\r\n\u003Cp\u003ESchool of Biological Sciences\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003EMadeline Mei\u003C\/strong\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EWill defend her dissertation\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003ER-Pyocin Regulation, Release, and Susceptibility in \u003Cem\u003EPseudomonas Aeruginosa\u003C\/em\u003E\u003C\/strong\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003ETuesday, October 25\u003Csup\u003Eth\u003C\/sup\u003E, 2022\u003C\/p\u003E\r\n\r\n\u003Cp\u003E9 AM EST\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EIn-person: The Dissertation Defense Room, 4th floor of Price Gilbert Library in room 4222\u003C\/p\u003E\r\n\r\n\u003Cp\u003EVirtual Link: \u003Ca href=\u0022https:\/\/gatech.zoom.us\/j\/91419037659\u0022\u003Ehttps:\/\/gatech.zoom.us\/j\/91419037659\u003C\/a\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003EPasscode: 964479\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003EThesis Advisor:\u003C\/strong\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003EStephen Diggle, Ph.D.\u003C\/p\u003E\r\n\r\n\u003Cp\u003ESchool of Biological Sciences\u003C\/p\u003E\r\n\r\n\u003Cp\u003EGeorgia Institute of Technology\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003ECommittee Members:\u003C\/strong\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003EMarvin Whiteley, Ph.D.\u003C\/p\u003E\r\n\r\n\u003Cp\u003ESchool of Biological Sciences\u003C\/p\u003E\r\n\r\n\u003Cp\u003EGeorgia Institute of Technology\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003ESam P. Brown, Ph.D.\u003C\/p\u003E\r\n\r\n\u003Cp\u003ESchool of Biological Sciences\u003C\/p\u003E\r\n\r\n\u003Cp\u003EGeorgia Institute of Technology\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EWilliam Ratcliff, Ph.D.\u003C\/p\u003E\r\n\r\n\u003Cp\u003ESchool of Biological Sciences\u003C\/p\u003E\r\n\r\n\u003Cp\u003EGeorgia Institute of Technology\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EJoana B Goldberg, Ph.D.\u003C\/p\u003E\r\n\r\n\u003Cp\u003EDepartment of Pediatrics\u003C\/p\u003E\r\n\r\n\u003Cp\u003EEmory University School of Medicine\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EABSTRACT:\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cem\u003EPseudomonas aeruginosa\u003C\/em\u003E is a Gram-negative opportunistic pathogen and a major determinant of declining lung function in individuals with cystic fibrosis (CF). \u003Cem\u003EP. aeruginosa\u003C\/em\u003E possesses many intrinsic antibiotic resistance mechanisms and isolates from chronic CF lung infections develop increasing resistance to multiple antibiotics over time. Chronic infection with \u003Cem\u003EP. aeruginosa\u003C\/em\u003E remains one of the main causes of mortality and morbidity in CF patients, thus new therapeutic interventions are necessary.\u003C\/p\u003E\r\n\r\n\u003Cp\u003ER-type pyocins are narrow spectrum, phage tail-like bacteriocins, specifically produced by \u003Cem\u003EP. aeruginosa\u003C\/em\u003E to kill other strains of \u003Cem\u003EP. aeruginosa\u003C\/em\u003E. Due to their specific anti-pseudomonal activity and similarity to bacteriophage, R-pyocins have potential as additional therapeutics for \u003Cem\u003EP. aeruginosa\u003C\/em\u003E, either in isolation, in combination with antibiotics, or as an alternative to phage therapy. There are five subtypes of R-pyocin (types R1-R5), and it is thought that each \u003Cem\u003EP. aeruginosa\u003C\/em\u003E strain uniquely produces only one of these, suggesting a degree of strain-specificity. \u003Cem\u003EP. aeruginosa\u003C\/em\u003E from CF lung infections develop increasing resistance to antibiotics, making new treatment approaches essential. It is known \u003Cem\u003EP. aeruginosa\u003C\/em\u003E populations in CF chronic lung infection become phenotypically and genotypically diverse over time, however, little is known of the efficacy of R-pyocins against heterogeneous populations. Even less is known regarding the timing and regulation of R-pyocins in CF lung infections, or if \u003Cem\u003EP. aeruginosa\u003C\/em\u003E utilizes R-pyocin production during infection for competition or otherwise \u0026ndash; which may influence pressure towards R-pyocin resistance.\u003C\/p\u003E\r\n\r\n\u003Cp\u003EIn this work, I evaluated R-pyocin type and susceptibility among \u003Cem\u003EP. aeruginosa\u003C\/em\u003E isolates sourced from CF infections and found that (i) R1-pyocins are the most prevalent R-type among respiratory infection and CF strains; (ii) a large proportion of \u003Cem\u003EP. aeruginosa\u003C\/em\u003E strains lack R-pyocin genes entirely; (iii) isolates from \u003Cem\u003EP. aeruginosa\u003C\/em\u003E populations collected from the same patient at a single time point have the same R-pyocin type; (iv) there is heterogeneity in susceptibility to R-pyocins within \u003Cem\u003EP. aeruginosa\u003C\/em\u003E populations and (v) susceptibility is likely driven by diversity of LPS phenotypes within clinical populations. These findings suggest that there is likely heterogeneity in response to other types of LPS-binding antimicrobials, including phage, which is important for consideration of antimicrobials as therapeutics.\u003C\/p\u003E\r\n\r\n\u003Cp\u003ETo investigate the prevalence of R2-pyocin susceptible strains in CF, I then utilized 110 isolates of \u003Cem\u003EP. aeruginosa\u003C\/em\u003E collected from five individuals with CF to test for R2-pyocin susceptibility and identify LPS phenotypes. From our collection we i) estimated that approximately 83% of sputum samples contain heterogenous P. aeruginosa populations without R2-pyocin resistant isolates and all sputum samples contained susceptible isolates; ii) we found that there is no correlation between R2-pyocin susceptibility and LPS phenotypes, and iii) we estimate that approximately 76% of isolates sampled from sputum lack O-specific antigen, 42% lack common antigen, and 27% exhibit altered LPS cores. This finding highlights that perhaps LPS packing density may play a more influential role in mediating R-pyocin susceptibility in infection. Finding the majority of our sampled \u003Cem\u003EP. aeruginosa \u003C\/em\u003Epopulations to be R2-pyocin susceptible further supports the potential of these narrow-spectrum antimicrobials despite facing heterogenous susceptibility among diverse populations.\u003C\/p\u003E\r\n\r\n\u003Cp\u003EIn order to evaluate how R-pyocins may influence strain competition and growth in CF lung infection, I assessed R-pyocin activity in an infection-relevant environment (Synthetic Cystic Fibrosis Sputum Medium; SCFM2) and found that (i) R-pyocins genes are transcribed more in the CF nutrient environment than in rich laboratory medium and (ii) in a structured, CF-like environment, R-pyocin induction is costly to producing strains in competition rather than beneficial. Our work suggests that R-pyocins may not be essential in CF lung infection and can be costly to producing cells in the presence of stress response-inducing stimuli, such as those commonly found in infection.\u003C\/p\u003E\r\n\r\n\u003Cp\u003EIn this thesis I have studied R-pyocin susceptibility, regulation and release utilizing a biobank of whole populations of \u003Cem\u003EP. aeruginosa\u003C\/em\u003E collected from 11 individuals with CF, as well as the CF infection model (SCFM) to understand the mechanisms of R-pyocin activity in an infection-relevant context and the role R-pyocins play in shaping \u003Cem\u003EP. aeruginosa\u003C\/em\u003E populations during infection. The findings of this work have illuminated the impact of \u003Cem\u003EP. aeruginosa\u003C\/em\u003E heterogeneity on R-pyocin susceptibility, furthered our understanding of R-pyocins as potential therapeutics, and built upon our knowledge of bacteriocin-mediated interactions.\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n","summary":null,"format":"limited_html"}],"field_subtitle":"","field_summary":"","field_summary_sentence":[{"value":"R-Pyocin Regulation, Release, and Susceptibility in Pseudomonas Aeruginosa"}],"uid":"27707","created_gmt":"2022-10-17 13:57:05","changed_gmt":"2022-10-17 13:57:05","author":"Tatianna Richardson","boilerplate_text":"","field_publication":"","field_article_url":"","field_event_time":{"event_time_start":"2022-10-25T10:00:00-04:00","event_time_end":"2022-10-25T12:00:00-04:00","event_time_end_last":"2022-10-25T12:00:00-04:00","gmt_time_start":"2022-10-25 14:00:00","gmt_time_end":"2022-10-25 16:00:00","gmt_time_end_last":"2022-10-25 16:00:00","rrule":null,"timezone":"America\/New_York"},"extras":[],"groups":[{"id":"221981","name":"Graduate Studies"}],"categories":[],"keywords":[{"id":"100811","name":"Phd Defense"}],"core_research_areas":[],"news_room_topics":[],"event_categories":[{"id":"1788","name":"Other\/Miscellaneous"}],"invited_audience":[{"id":"78761","name":"Faculty\/Staff"},{"id":"78771","name":"Public"},{"id":"78751","name":"Undergraduate students"}],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[],"email":[],"slides":[],"orientation":[],"userdata":""}}}