Accelerated evolution of antibiotic resistance in a bacterial swarm

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Accelerated evolution of antibiotic resistance in a bacterial swarm Many bacterial species band together as a dense collective and migrate over surfaces in a process called swarming. Swarms exhibit high tolerance to a broad class of antibiotics, reminiscent of the tolerance seen in biofilms and other settings. Unlike the latter environments however, where slower bacterial growth rates and lower metabolic activity are implicated in the higher tolerance to drug treatment, bacterial swarms are metabolically highly active and grow robustly. Thus, the tolerance exhibited by swarms is apparently distinct from the other reported cases of this phenomenon. We made significant recent progress in understanding tolerance in E. coli swarms when we discovered that swarms are intrinsically programmed to upregulate expression of multiple drug efflux pumps and of ROS pathways that protect against antibiotic stress. At the same time, swarms also downregulate expression of genes involved in mismatch and base-excision DNA repair pathways. Consistent with this observation, preliminary data show that swarms have higher mutation rates and are more proficient at evolving genetic resistance to antibiotics compared to their planktonic counterparts. The fitness cost associated with higher mutation rates apparently outweighs the advantage of evolvability to genetic resistance. We propose to investigate how the intrinsic program for upregulating Efflux pathways unfolds. We also propose to investigate the link between upregulation of Efflux and downregulation of DNA repair pathways. Interfering with evolvability to resistance, hence tolerance, is perhaps as important as combating resistance itself. Investigation of the underlying tolerance mechanisms may in the future, lead to genetic or physiology-based markers for diagnosis, treatment, and eradication.