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Investigating the Impact of Antibiotic-Induced Cryptic Plasmid Copy Number Increase on Cryptic Plasmid Mobilization Rate
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. (Dan Andersson)
2026 (English)Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
Abstract [en]

Heteroresistance is a bacterial phenotype where subpopulations of bacteria with lower antibiotic susceptibility than the main population are present. In clinical settings, this phenotype poses a problem as common methods used to determine antibiotic susceptibility are poor at detecting it which can affect treatment negatively. Research has implicated resistance encoding cryptic plasmids (CP) in heteroresistance via their ability to increase in plasmid copy number (PCN) under antibiotic selective pressure and mobilize with the help of large conjugative plasmids. This study aimed to further investigate if increased cryptic PCN induced by antibiotics influences the mobilization frequency of the CP like preliminary data indicated. Lambda red was used to introduce the trimethoprim resistance gene dhfr onto selected CP. A recently developed high throughput conjugation method where mating takes place in broth, was then used to perform mobilization experiments where recombinant bacterial strains were selected with antibiotic for increased cryptic PCN. Unfortunately, an inoculum effect from chloramphenicol was observed due to the chloramphenicol resistant recipient. Because of this inoculum effect, it was not possible to determine the impact of antibiotic induced increased cryptic PCN on the rate of mobilization. Despite this, the study gave important insight into how the experimental system could be improved. Future studies could introduce an alternative selective marker in the recipient strain to enable large scale data collection. The high throughput conjugation method used in the study shows great promise as it was highly efficient and would likely enable consistent data collection once the proposed measures are implemented.

Place, publisher, year, edition, pages
2026.
Keywords [en]
Cryptic plasmids, heteroresistance, antibiotic resistance, mobilization, conjugation
National Category
Microbiology
Identifiers
URN: urn:nbn:se:uu:diva-595620OAI: oai:DiVA.org:uu-595620DiVA, id: diva2:2092798
Educational program
Master Programme in Infection Biology
Supervisors
Examiners
Available from: 2026-08-18 Created: 2026-08-17 Last updated: 2026-08-18Bibliographically approved

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