{"693953":{"#nid":"693953","#data":{"type":"event","title":"PhD Defense by Isaac Estrada","body":[{"value":"\u003Cp\u003EIn partial fulfillment of the requirements for the degree of\u003C\/p\u003E\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\u003Cp\u003EDoctor of Philosophy in Biology\u003C\/p\u003E\u003Cp\u003EIn the\u003C\/p\u003E\u003Cp\u003ESchool of Biological Sciences\u003C\/p\u003E\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003EIsaac Estrada\u003C\/strong\u003E\u003C\/p\u003E\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\u003Cp\u003EWill defend his dissertation\u003C\/p\u003E\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003EDefining and Engineering R-pyocins as Targeted Antimicrobials against Multidrug-Resistant \u003C\/strong\u003E\u003Cem\u003E\u003Cstrong\u003EPseudomonas aeruginosa\u003C\/strong\u003E\u003C\/em\u003E\u003C\/p\u003E\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\u003Cp\u003E23rd, November, 2026\u003C\/p\u003E\u003Cp\u003E3pm\u003C\/p\u003E\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003EMicrosoft Teams meeting\u003C\/strong\u003E\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003EJoin:\u0026nbsp;\u003C\/strong\u003E\u003Ca href=\u0022https:\/\/teams.microsoft.com\/meet\/242094461672285?p=tkn3wkcQrcQ9LBhWbE\u0022 target=\u0022_blank\u0022 title=\u0022Meeting join\u0022\u003Ehttps:\/\/teams.microsoft.com\/meet\/242094461672285?p=tkn3wkcQrcQ9LBhWbE\u003C\/a\u003E\u003C\/p\u003E\u003Cp\u003EMeeting ID: 242 094 461 672 285\u003C\/p\u003E\u003Cp\u003EPasscode: Jv9pr6TC\u003C\/p\u003E\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003EThesis Advisor:\u003C\/strong\u003E\u003C\/p\u003E\u003Cp\u003ESteve Diggle, Ph.D.\u003C\/p\u003E\u003Cp\u003ESchool of Biological Sciences\u003C\/p\u003E\u003Cp\u003EGeorgia Institute of Technology\u003C\/p\u003E\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003ECommittee Members:\u003C\/strong\u003E\u003C\/p\u003E\u003Cp\u003ESam Brown, Ph.D.\u003C\/p\u003E\u003Cp\u003ESchool of Biological Sciences\u003C\/p\u003E\u003Cp\u003EGeorgia Institute of Technology\u003C\/p\u003E\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\u003Cp\u003EMarvin Whiteley, Ph.D.\u003C\/p\u003E\u003Cp\u003ESchool of Biological Sciences\u003C\/p\u003E\u003Cp\u003EGeorgia Institute of Technology\u003C\/p\u003E\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\u003Cp\u003EJoanna Goldberg, Ph.D.\u003C\/p\u003E\u003Cp\u003EDepartment of Pediatrics\u003C\/p\u003E\u003Cp\u003EDivision of Pulmonary, Asthma, Cystic Fibrosis, and Sleep\u003C\/p\u003E\u003Cp\u003EEmory University School of Medicine\u003C\/p\u003E\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\u003Cp\u003EKendra Rumbaugh, Ph.D.\u003C\/p\u003E\u003Cp\u003EDepartment of Surgery\u003C\/p\u003E\u003Cp\u003E\u003Cem\u003ETexas Tech University Health Sciences Center\u003C\/em\u003E\u003C\/p\u003E\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\u003Cp\u003EABSTRACT:\u003C\/p\u003E\u003Cp\u003EDefining and Engineering R-pyocins as Targeted Antimicrobials\u003C\/p\u003E\u003Cp\u003Eagainst Multidrug-Resistant \u003Cem\u003EPseudomonas aeruginosa\u003C\/em\u003E\u003C\/p\u003E\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\u003Cp\u003EIsaac Estrada\u003C\/p\u003E\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\u003Cp\u003E298 Pages\u003C\/p\u003E\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\u003Cp\u003EDirected by Dr. Stephen P. Diggle\u003C\/p\u003E\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\u003Cp\u003E\u003Cem\u003EPseudomonas aeruginosa\u003C\/em\u003E is one of the most difficult organisms to treat, and the high-risk clonal lineages disseminated worldwide leave few treatment options. R-type pyocins are narrow-spectrum, phage tail-like bacteriocins produced by \u003Cem\u003EP. aeruginosa\u003C\/em\u003E to kill other strains of the same species and are currently classified into three main subtypes (R1, R2, and R5). They have been proposed as therapeutic agents for many years, and their mechanism of action is well understood. Their full killing specificity, their activity in infected tissue, and the purity of current preparations, however, remain poorly characterized.\u003C\/p\u003E\u003Cp\u003EIn this work, we evaluated R-pyocin distribution and killing specificity across a clinical biobank of high-risk strains. Screening 1,086 genomes and the 100-strain high-risk clinical panel, we find that O-specific antigen serotype predicts R-pyocin subtype independent of clonal background, and that killing spectrum tracks tail fiber allelic variation rather than the subtype classification currently in use.\u003C\/p\u003E\u003Cp\u003ETo determine how resistance to R-pyocins arises and how far it extends, we subjected laboratory strains and a pan-drug-resistant wound isolate to sustained R-pyocin selection. Resistance evolved rapidly, and sequenced resistant variants were cross-resistant to all subtypes.\u0026nbsp;We found that resistance is gained via a large chromosomal deletion that removed \u003Cem\u003EgalU, \u003C\/em\u003Ewhich is essential for the formation of the R-pyocin receptor\u003Cem\u003E.\u0026nbsp;\u003C\/em\u003EThe same deleted region carries the \u003Cem\u003EmexXY\u003C\/em\u003E efflux operon together with virulence and biofilm loci, so surviving mutants are resensitized to aminoglycosides, unable to form biofilms, and avirulent. Resistance to R-pyocins is therefore itself a therapeutic advantage.\u003C\/p\u003E\u003Cp\u003ETo evaluate how much activity is retained from \u003Cem\u003Ein vitro\u003C\/em\u003E assays to \u003Cem\u003Ein vivo\u003C\/em\u003E infection, we tested fixed-dose preparations across increasingly complex systems: broth and wound media, a collagen biofilm matrix, explanted infected wound tissue, and a murine pulmonary infection. We found that activity is limited by access to the bacteria and contact time rather than by intrinsic potency.\u003C\/p\u003E\u003Cp\u003ELastly, to determine whether R-pyocin preparations are cytotoxic to mammalian cells, and whether any cytotoxicity is a property of the particle itself, we applied nine independently produced preparations to three mammalian cell lines. Toxicity tracked the preparation rather than the subtype and could not be attributed to any property of the particle, indicating that current preparation methods cannot reliably produce non-cytotoxic R-pyocins. We therefore engineered a hexahistidine tag into the collar protein encoded by PA0615 and captured assembled particles from crude lysate in a single affinity chromatography step.\u003C\/p\u003E\u003Cp\u003EOverall, this work demonstrates that the limits on R-pyocin therapy are set by specificity, delivery, and purity of preparation rather than by the killing machinery itself. These findings, along with the affinity-tagged particle, provide the basis for TAILSTRIKE, a proposed plasmid-encoded chassis that separates the killing machinery from an exchangeable targeting module, allowing narrow-spectrum antimicrobials to be customized to a chosen target.\u003C\/p\u003E\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E","summary":"","format":"limited_html"}],"field_subtitle":"","field_summary":[{"value":"\u003Cp\u003E\u003Cstrong\u003EDefining and Engineering R-pyocins as Targeted Antimicrobials against Multidrug-Resistant \u003C\/strong\u003E\u003Cem\u003E\u003Cstrong\u003EPseudomonas aeruginosa\u003C\/strong\u003E\u003C\/em\u003E\u003C\/p\u003E","format":"limited_html"}],"field_summary_sentence":[{"value":"Defining and Engineering R-pyocins as Targeted Antimicrobials against Multidrug-Resistant Pseudomonas aeruginosa"}],"uid":"27707","created_gmt":"2026-11-10 16:34:57","changed_gmt":"2026-11-10 16:35:28","author":"Tatianna Richardson","boilerplate_text":"","field_publication":"","field_article_url":"","field_event_time":{"event_time_start":"2026-11-23T15:00:00-05:00","event_time_end":"2026-11-23T17:00:00-05:00","event_time_end_last":"2026-11-23T17:00:00-05:00","gmt_time_start":"2026-11-23 20:00:00","gmt_time_end":"2026-11-23 22:00:00","gmt_time_end_last":"2026-11-23 22:00:00","rrule":null,"timezone":"America\/New_York"},"location":"Microsoft Teams ","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":"78771","name":"Public"}],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[],"email":[],"slides":[],"orientation":[],"userdata":""}}}