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A Bacterial Pathogen Induces Reversible Developmental Slowing by High Reactive Oxygen Species and Mitochondrial Damage in Caenorhabditis Elegans
Authors
Mirza, ZeynepFaculty Advisor
Victor Ambros, Ph.D.; Marian Walhout, Ph.D.Academic Program
Interdisciplinary Graduate ProgramUMass Chan Affiliations
Morningside Graduate School of Biomedical SciencesDocument Type
Doctoral DissertationPublication Date
2023-08-28
Metadata
Show full item recordAbstract
Host-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.DOI
10.13028/3b5v-fg49Permanent Link to this Item
http://hdl.handle.net/20.500.14038/52484Rights
Copyright © 2023 Zeynep MirzaDistribution License
All Rights Reservedae974a485f413a2113503eed53cd6c53
10.13028/3b5v-fg49