The role of physical interactions in shaping the genetic diversity of spatially expanding phage and bacterial populations

Natural microbial populations often feature complex interactions between individuals of the same species, different species, and different domains of life. In addition, isogenic microbial populations can display immense phenotypic heterogeneity leading to division of labour and seemingly cooperative behaviour. The effect of such interactions on the evolution of microbial populations, particularly those that are expanding in space, remains an open question. I investigate this effect using two distinct biological systems. First, I examine viral-host dynamics in bacteriophages, viruses that infect bacteria. Second, I explore the impact of phenotypic heterogeneity within B. subtilis biofilms during expansions on solid-air interfaces. I consider the scenario of a lytic phage which replicates by infecting a lawn of bacteria. The physical interactions that occur during the lytic life-cycle have profound effects on the evolution of the phage. Using stochastic simulations and an analytic calculation of the rate of diversity loss, I find the strength of implicit density-dependence at which the scaling between the effective population and the total viral population maps to that of semi-pushed and pushed sFKPP waves. I additionally find that the shape of the viral expansion profile, patterns of ancestry, and rate of diversity loss in viral expansions can be independently tuned by multiple population genetic parameters, unlike sFKPP waves. I also present work in which I attempt to ascertain a genetic signature of pushed-waves from 2D expansions using stochastic simulations. I also examine bacterial biofilms with a special attention to the in vitro system of B. subtilis, a model biofilm-former which characteristically displays wrinkle formation. I show that wrinkles, by virtue of supporting liquid channels beneath their surface, allow for the escape of initially trapped clones during spatial expansions, a process that requires phenotypic heterogeneity and wrinkle formation. I additionally explore the mechanical properties of these wrinkles using a molecular dynamics model of wrinkle formation. Finally, I show that the morphology of the edge of expanding biofilms invading obstacles is sensitive to physical factors which feed back on the observed phenotype of cells at the edge, and again model this using molecular dynamical simulations.

Name dc:type.qualificationname

Doctor of Philosophy (PhD)

Level dc:type.qualificationlevel

Doctoral

Grantor dc:publisher.institution

University of Cambridge

Year dc:date.issued

2024

Author dc:creator

• Krishnan, Nikhil

Advisor dc:contributor.advisor

• Fusco, Diana

• bacillus
• bacteriophage
• biofilms
• evolution

Licence

• https://www.repository.cam.ac.uk/bitstreams/231d83a9-3164-43f1-b1a6-1fd358e5ef88/download
• https://creativecommons.org/licenses/by-nc/4.0/

Language dc:language

eng

DOI dc:identifier.doi

https://doi.org/10.17863/CAM.121705

OAI identifier oai:identifier

oai:www.repository.cam.ac.uk:1810/390002