Group motility as a mechanism of self-defence in bacteria

Programme overview:
This MRC-funded doctoral training partnership (DTP) brings together cutting-edge molecular and analytical sciences with innovative computational approaches in data analysis to enable students to address hypothesis-led biomedical research questions. This is a 4-year programme whose first year involves a series of taught modules and two laboratory-based research projects that lead to an MSc in Interdisciplinary Biomedical Research. The first two terms consist of a selection of taught modules that allow students to gain a solid grounding in multidisciplinary science. Students also attend a series of masterclasses led by academic and industry experts in areas of molecular, cellular and tissue dynamics, microbiology and infection, applied biomedical technologies and artificial intelligence and data science. During the third and summer terms students conduct two eleven-week research projects in labs of their choice.

Project:
Antibiotic resistance is the ability of bacteria to resist the effects of medication used to treat them. One of the least understood mechanisms by which bacteria gain resistance is physical adaptation. An example of such adaptation is produced when bacteria move as swarms instead of as individuals under certain conditions of surface wetness and stiffness. These swarms consist in flagella-driven bacteria which expand over the surface at fast speed and invade larger regions than the swimming counterparts in the presence of antibiotics.

Understanding how swarming motility is triggered and the physical mechanism of defense will provide us with methods to cease the swarming formation and to overcome these physical barriers which confer the resistance.

Swarming starts with the expression of a specific phenotype at individual cell level which leads to a group phenomenon. The increase in resistance to antibiotic is hence supposed to be originated by this interplay between both scales. Thus, to address this problem, we will take an interdisciplinary approach combining molecular microbiology, cellular biophysics, and computational simulations.

A dual-scale set up which combines data acquisition at both, colony and single-cell level scale will be developed and completed during the first stages of the project. Then, swarming dynamics will be studied in both scales when bacteria are exposed to different environmental conditions (sort and concentration of antibiotic, temperature, etc.). In parallel, a mathematical model will be developed to find out the physical mechanisms underlying the increase in resistance due to swarming motility. Finally, studies will focus on the response at chemical stress at single cell level which will determine swarmers' history of antibiotic exposure.