Abstract
The emergence and spread of bacterial infections that are resistant to antibiotic treatment, combined with the lack of development of new antibiotics, pose a global health problem that is now well recognised. Tackling antimicrobial resistance (AMR) requires coordinated, cross-disciplinary effort: relevant themes include clinical medicine, microbiology, diagnostics, drug discovery, epidemiology, evolutionary biology, global public health policy, veterinary science and agriculture. Physicists can make important contributions to the understanding of the fundamental science of how antibiotics work and how resistance to them can emerge. For instance, at the level of bacterial populations, physical interactions between cells and their environment shape the self-assembly of spatially-structured bacterial conglomerates such as biofilms. From a physics point of view, the interplay between biological phenomena such as growth and physical phenomena such as chemical diffusion and physical forces provides many interesting questions. Other population-level phenomena of interest to physicists include stochastic differences in the behaviour of individual cells, caused by noise in gene expression, which can have drastic consequences for the response of the population to antibiotic treatment. The goal of the dissertation is to review the principal models used in AMR modelling, with a particular focus on those which emphasize the role of stochasticity. Indeed, stochasticity in the molecular processes involved in gene expression brings about phenotypic heterogeneity which is central in producing antibiotic resistance. From this perspective, a particularly important example of phenotypic heterogeneity is the existence within bacterial populations of a subpopulation of ‘‘persister cells’’ which can survive antibiotic treatment. For instance, some experiments using microfluidic devices (Balaban et al) have highlighted E. coli cells switching into and out of a non-growing persister state. Why these bacteria prefer to take this behaviour? Although the molecular mechanisms controlling this switch are still poorly understood and they form the topic of active research, there is also a need to develop simple and powerful models which can explain some experiments. Towards the end of the project we will investigate the role of heterogeneity and how this can be beneficial for populations spreading in space.
Possible collaborations include E. Crooks (University of Swansea, UK), S. Mitri (Université de Lausanne, CH) and S. Klumpp (University of Göttingen, DE).
References
- Allen, R. and Waclaw, B., 2016. ‘‘Antibiotic resistance: a physicist’s view’’. Physical biology, 13(4), p.045001.
- Further papers by E. Crooks, J. Jimenez and S. Klumpp.
