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dc.contributor.advisorVictor Ambros, Ph.D.en_US
dc.contributor.advisorMarian Walhout, Ph.D.en_US
dc.contributor.authorMirza, Zeynep
dc.date.accessioned2023-09-11T14:02:14Z
dc.date.available2023-09-11T14:02:14Z
dc.date.issued2023-08-28
dc.identifier.doi10.13028/3b5v-fg49en_US
dc.identifier.urihttp://hdl.handle.net/20.500.14038/52484
dc.description.abstractHost-pathogen interactions are complex by nature, and the host developmental stage increases this complexity. Development is an energetically demanding period when biomass production and cell differentiation events occur. We investigated how a developing organism copes with the additional energy-expensive burden of pathogen stress during this crucial period. We explored this question by utilizing Caenorhabditis elegans larvae as the host and the bacterium Pseudomonas aeruginosa as the pathogen. By screening 36 P. aeruginosa isolates, we found that the CF18 strain causes a severe but reversible developmental delay. CF18 slows larval development via induction of reactive oxygen species (ROS) and mitochondrial dysfunction. In response, the larvae upregulate mitophagy and antimicrobial and detoxification genes; however, mitochondrial unfolded protein response (UPRmt) is repressed. Consistent with these observations, antioxidant or iron supplementation or the removal of larvae from CF18 rescues developmental delay, mitochondrial damage, and high ROS. We examined the virulence factors of CF18 required for developmental delay via transposon mutagenesis, RNA-sequencing, and candidate gene deletion approaches. Our results showed that virulence factors regulated by quorum sensing and the GacA/S system were responsible for developmental slowing. We also demonstrated that well-studied mitochondrial toxins of P. aeruginosa, phenazines and hydrogen cyanide, are not required for CF18-induced developmental slowing. This study highlights the importance of ROS levels and mitochondrial health as determinants of developmental rate and how pathogens can attack these important features.en_US
dc.language.isoen_USen_US
dc.publisherUMass Chan Medical Schoolen_US
dc.rightsCopyright © 2023 Zeynep Mirzaen_US
dc.rights.uriAll Rights Reserveden_US
dc.subjectC. elegansen_US
dc.subjectmitochondriaen_US
dc.subjectP. aeruginosaen_US
dc.subjectROSen_US
dc.subjectdevelopmenten_US
dc.titleA Bacterial Pathogen Induces Reversible Developmental Slowing by High Reactive Oxygen Species and Mitochondrial Damage in Caenorhabditis Elegansen_US
dc.typeDoctoral Dissertationen_US
atmire.contributor.authoremailZeynep.Mirza@umassmed.eduen_US
dc.contributor.departmentMorningside Graduate School of Biomedical Sciencesen_US
dc.description.thesisprogramInterdisciplinaryen_US
dc.identifier.orcid0000-0002-4553-6509en_US


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