Bacterial biofilm development in response to toxic molecules

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Most bacteria grow in surface-associated communities called biofilms, a mode of growth that protects them from predators and noxious substances, including detergents, antibiotics, and toxic metals. The signals and pathways that modulate biofilm development in response to chemical exposure are poorly understood, even though biofilms play key roles in the environment, agriculture, and animal/human well-being. We showed previously that exposure of bacteria to sublethal concentrations of diverse antimicrobials, detergents, and disinfectants stimulates biofilm formation. For some compounds, biofilm stimulation occurred at concentrations far below those that impacted growth, suggesting that bacteria detect minute amounts of potentially dangerous molecules and respond with increased biofilm formation. We propose that increases in biofilm formation are a rapid protective response to mitigate damage to the population. This non-specific response is reminiscent of the innate immune responses of higher organisms, and likely buys time so the population can subsequently develop more classical forms of resistance. Based on preliminary studies, our working hypothesis is that exposure to sub-MIC antibiotics, detergents, or disinfectants causes cellular damage that triggers stress responses, increasing metabolic demand to repair this damage. It is not yet clear how these responses are linked to increased levels of biofilm. We will compare two model species, P. aeruginosa and Escherichia coli for which we have a wealth of tools, to make more generalized conclusions about biofilm stimulation. In prior NSERC-funded studies, we identified mutants that failed to increase biofilm formation when exposed to various antimicrobials. Each species yielded a short list of interesting mutants that we will further characterize to understand how and why they fail to respond to these chemical cues. Our data suggest that sub-MIC antibiotics cause damage whose repair increases energy (ATP) demand and thus respiration. We will determine how these demands for increased metabolic capacity are linked to production of more biofilm, which requires increased synthesis of matrix components. Our specific aims are to: 1) Characterize the biofilm stimulation responses of P. aeruginosa and E. coli wild type and respiratory mutants when exposed to sub-MIC antibiotics in the presence of alternative electron acceptors 2) Investigate the links between aerobic central metabolism, cyclic-di-GMP levels, and production of biofilm matrix polysaccharide components This work will provide new understanding of biofilm biology and the ways in which bacteria perceive and respond to bioactive small molecules. There are many scenarios where increased biofilm formation is desirable - for example, wastewater treatment, extraction of low-concentration minerals from mine tailings, or plant root colonization for growth promotion - and our work may provide clues on how to more easily achieve this goal.