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Biophysical mechanisms of antimicrobial resistance in swarming B. subtilis
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Grobas, Iago (2021) Biophysical mechanisms of antimicrobial resistance in swarming B. subtilis. PhD thesis, University of Warwick.
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Official URL: http://webcat.warwick.ac.uk/record=b3764616
Abstract
Swarms and biofilms are the two major modes of bacterial collectives and confer cells with emergent properties that lack as individuals, such as an increase in antibiotic tolerance. Swarming is a rapid type of surface colonization, and therefore its ability to withstand high antibiotic concentrations could lead to the subsequent establishment of high lyre- silient biofilms orgenetically resistant bacteria in regions that could not otherwise have been colonized. However, whether the development of biofilms or resistant microcolonies by swarms is possible is unknown. Using swarming Bacillus subtilis, we reveal that a biophysical mechanism, reminiscent of motility-induced phase separation (MIPS),under- pins a swarming-to-biofilm transition through a localized dynamic phase transition. This transition, triggered by an external stressor, is underpinned by a localized multilayer formation. Inspired by the thermodynamic properties of active matter, we demonstrated that such multilayer formation forms through a nucleation and growth process near an antibiotic gradient, and through spinodal decomposition in absence of stress. The nucle- ation and growth of multiple layers near the antibiotic, triggers waves of bacteria that move towards the antibiotic source, suggesting a novel mechanism of bacterial transport. When swarming to biofilm transition was prohibited by the environmental conditions, the swarm uses an alternative strategy to cope with the antibiotic gradient by developing re- sistant microcolonies. Quantification of this resistance displayed that the higher resistance to kanamycinis acquired together with resistance to other antibiotics targeting the same process. Inspired by the medical motivation of this project, we suggested solutions to both the emergence of the biofilm and the development of resistant bacteria by using the insight that we gained throughout the study. In particular, we proved that the biofilm formation can be reduced when splitting the total dose of antibiotics in two different time steps: the first triggers the multi layer formation and the second targets this key region in the swarm. Alternatively, when the swarm develops resistant colonies, we observed that these become more vulnerable to other drugs, so a tratement using certain sequence of antibiotics could be highly effective to kill multi drug resistant bacteria. These could lead to new strategies to tackle antimicrobial resistance.
Item Type: | Thesis (PhD) | ||||
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Subjects: | Q Science > QD Chemistry Q Science > QR Microbiology |
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Library of Congress Subject Headings (LCSH): | Drug resistance in microorganisms, Biofilms, Microbial aggregation, Bacillus subtilis, Nucleation, Bacteria -- Motility | ||||
Official Date: | 4 October 2021 | ||||
Dates: |
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Institution: | University of Warwick | ||||
Theses Department: | School of Life Sciences ; Warwick Medical School | ||||
Thesis Type: | PhD | ||||
Publication Status: | Unpublished | ||||
Supervisor(s)/Advisor: | Asally, Munehiro ; Polin, Marco | ||||
Format of File: | |||||
Extent: | 168 leaves : illustrations | ||||
Language: | eng |
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