Screening and Characterization of Antimicrobial Compounds and Material against Vibrio cholerae

Kim, Haeun (Sara)

Screening and Characterization of Antimicrobial Compounds and Material against Vibrio cholerae

dc.contributor.advisor	MacDonald, Justin A.
dc.contributor.advisor	Dong, Tao G.
dc.contributor.author	Kim, Haeun (Sara)
dc.contributor.committeemember	DeVinney, Rebekah
dc.contributor.committeemember	Schriemer, David
dc.date	2023-11
dc.date.accessioned	2023-10-17T17:00:30Z
dc.date.available	2023-10-17T17:00:30Z
dc.date.issued	2023-10-12
dc.description.abstract	Antibiotic resistance (ABR) is a multisectoral global threat. With an increasing number of critical pathogens acquiring resistance against multiple classes of antibiotics, we face the terror of the post-antibiotic era. Vibrio cholerae, the cholera-causing pathogen, is no exception to the menace of multi-drug resistance. Strains from worldwide outbreaks have shown resistance to all antibiotics used to treat cholera, including ciprofloxacin. With cholera being prevalent in developing countries and regions affected by natural and anthropogenic disasters, an increase in fatalities is a rising concern in these areas with the number of effective antibiotics rapidly decreasing. This thesis explores the alternative approaches to treating cholera and controlling the spread of ABR pathogens in the environment. First, a library of 400 chemical compounds with antimicrobial activities, the Pathogen Box, is screened for compounds that exhibit killing or inhibiting activities against V. cholerae. Two compounds, MMV687807 and MMV675968, demonstrated bactericidal and bacteriostatic activity against the pathogen with high efficacy, respectively. RNA-seq analyses of V. cholerae treated with each compound revealed that their impact on multiple cellular functions, including carbon metabolism and iron homeostasis. Whole genome sequencing of spontaneous resistance mutants uncovered that activation of an efflux system via mutation to their regulator confers resistance to MMV687807. MMV675968 was identified to function similar to trimethoprim, targeting the dihydrofolate reductase of V. cholerae. This compound has the potential to be developed as a trimethoprim replacement with a minimum inhibitory concentration lower by 14-fold. Next, the antibacterial property of a newly synthesized cellulose aerogel cross-linked with different concentrations of silver/lignin nanoparticles (lignin only, 1Ag/L, 2Ag/L, and 3Ag/L) was studied in collaboration with Xiao He. Each aerogel was incubated with Gram-positive or Gram-negative pathogens, and surviving colonies were counted. Increase in killing efficiency was observed with increasing concentration of Ag/L nanoparticles. The cellulose aerogel with 3 Ag/L exhibited exceptional killing across all tested species: E. coli: > 99.99%, P. aeruginosa: > 99.9%, V. cholera: > 99.99%, S. aureus: > 99.99%, B. subtilis: > 97.4%. Through screening small molecules and exploring synthetic material cross-linked with nanoparticles, this thesis demonstrates the significance of developing new tools to inhibit bacterial pathogens and fight the spread of ABR.
dc.identifier.citation	Kim, H. (2023). Screening and characterization of antimicrobial compounds and material against Vibrio cholerae (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.
dc.identifier.uri	https://hdl.handle.net/1880/117387
dc.identifier.uri	https://doi.org/10.11575/PRISM/42230
dc.language.iso	en
dc.publisher.faculty	Graduate Studies
dc.publisher.institution	University of Calgary
dc.rights	University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.
dc.subject	Vibrio cholerae
dc.subject	Antibiotic resistance
dc.subject	Silver nanoparticles
dc.subject	Cellulose aerogel
dc.subject	Pathogen Box
dc.subject	Cholera
dc.subject	Small molecules
dc.subject	Antibiotic
dc.subject.classification	Microbiology
dc.subject.classification	Biology--Molecular
dc.title	Screening and Characterization of Antimicrobial Compounds and Material against Vibrio cholerae
dc.type	master thesis
thesis.degree.discipline	Medicine – Biochemistry and Molecular Biology
thesis.degree.grantor	University of Calgary
thesis.degree.name	Master of Science (MSc)
ucalgary.thesis.accesssetbystudent	I do not require a thesis withhold – my thesis will have open access and can be viewed and downloaded publicly as soon as possible.