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Oliveira, N. M.

Publications and source records attributed to Oliveira, N. M..

4 recordsLinked to original sources

Bacterial motility governs the evolution of antibiotic resistance in spatially heterogeneous environments

Bacteria evolving in natural and clinical settings experience spatial fluctuations of multiple factors and this heterogeneity is expected to affect bacterial adaptation. Notably, spatial heterogeneity in antibiotic concentrations is believed to accelerate the evolution of antibiotic resistance. However, current literature overlooks the role of cell motility, which is key for bacterial survival and reproduction. Here, we consider a quantitative model for bacterial evolution in antibiotic gradients, where bacteria evolve under the stochastic processes of proliferation, death, mutation and migration. Numerical and analytical results show that cell motility has major effects on bacterial adaptation. If migration is relatively rare, it accelerates adaptation because resistant mutants can colonize neighbouring patches of increasing antibiotic concentration avoiding competition with wild-type cells; but if migration is common throughout the lifespan of bacteria, it decelerates adaptation by promoting genotypic mixing and ecological competition. If migration is sufficiently high, it can limit bacterial survival, and we derive conditions for such a regime. Similar patterns are observed in more complex scenarios, namely where bacteria can bias their motion or switch between motility phenotypes either stochastically or in a density-dependent manner. Overall, our work reveals limits to bacterial adaptation in antibiotic landscapes that are set by cell motility.

microbiology↗

Suicidal chemotaxis in bacteria

Bacteria commonly live in communities on surfaces where steep gradients of antibiotics and other chemical compounds routinely occur. While many species of bacteria can move on surfaces, we know surprisingly little about how such antibiotic gradients affect cell motility. Here we study the behaviour of the opportunistic pathogen Pseudomonas aeruginosa in stable spatial gradients of a range of antibiotics by tracking thousands of cells in microfluidic devices as they form biofilms. Unexpectedly, these experiments reveal that individual bacteria use pili-based ( twitching) motility to actively navigate towards regions with higher antibiotic concentrations. Our analyses suggest that this biased migration is driven, at least in part, by a direct response to the antibiotics. Migrating cells can reach antibiotic concentrations hundreds of times higher than their minimum inhibitory concentration in a few hours and remain highly motile. However, isolating these cells - using fluid-walled microfluidic devices that can be reconfigured in situ - suggests that these bacteria are terminal and not able to reproduce. In spite of moving towards their death, we show that migrating cells are capable of entering a suicidal program to release bacteriocins that are used to kill other bacteria. Our work suggests that bacteria respond to antibiotics as if they come from a competing colony growing in the neighbourhood, inducing them to invade and attack. As a result, clinical antibiotics have the potential to serve as a bait that lures bacteria to their death.

microbiology↗

Stabilization of Microbial Communities by Responsive Phenotypic Switching

Clonal microbes can switch between different phenotypes and recent theoretical work has shown that stochastic switching between these subpopulations can stabilize microbial communities. This phenotypic switching need not be stochastic, however, but could also be in response to environmental factors, both biotic and abiotic. Here, motivated by the bacterial persistence phenotype, we explore the ecological effects of such responsive switching by analyzing phenotypic switching in response to competing species. We show that the stability of microbial communities with responsive switching differs generically from that of communities with stochastic switching only. To understand the mechanisms by which responsive switching stabilizes coexistence, we go on to analyze simple two-species models. Combining exact results and numerical simulations, we extend the classical stability results for the competition of two species without phenotypic variation to the case in which one species switches, stochastically and responsively, between two phenotypes. In particular, we show that responsive switching can stabilize coexistence even when stochastic switching on its own does not affect the stability of the community.

biophysics↗

Biofilm Growth Under Elastic Confinement

Bacteria often form surface-bound communities, embedded in a self-produced extracellular matrix, called biofilms. Quantitative studies of their growth have typically focused on unconfined expansion above solid or semi-solid surfaces, leading to exponential radial growth. This geometry does not accurately reflect the natural or biomedical contexts in which biofilms grow in confined spaces. Here we consider one of the simplest confined geometries: a biofilm growing laterally in the space between a solid surface and an overlying elastic sheet. A poroelastic framework is utilised to derive the radial growth rate of the biofilm; it reveals an additional self-similar expansion regime, governed by the stiffness of the matrix, leading to a finite maximum radius, consistent with our experimental observations of growing Bacillus subtilis biofilms confined by PDMS.

biophysics↗