Sub-Lethal Exposures to Metal and Metal-Oxide Nanoparticles Lead to Antibiotic Resistance in Engineered Environments: A Mechanistic Study

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The safety of engineered nanomaterials and antibiotic resistance are two issues of global concern. Nanomaterials are particles materials that have a diameter on the nanometer scale, and they are used widely in industry and in consumer products. However, some nanomaterials have been shown to kill beneficial bacteria. Antibiotic resistance is the ability of microorganisms to deactivate antibiotics, thus allowing harmful bacteria to survive. The effects of antibiotic resistance create an estimated billion-dollar in annual costs to the United States economy. This research project will study the question of whether nanomaterials can stimulate antibiotic resistance in disease-causing bacteria. These investigations will be accomplished through multi-phase experimental studies to identify toxic concentrations of nanomaterials and to characterize the adaptive responses of microorganisms to nanomaterials. Successful completion of this project will advance our understanding of how nanomaterials stimulate antibiotic resistance. The researchers will develop an interdisciplinary undergraduate course on antibiotic resistance that incorporates an expert panel discussion on antibiotic resistance, a lab module on adaptive resistance, and student-produced podcasts that address challenges in antibiotic resistance. Multiple undergraduate students will be engaged in the research activities through the Graduates Linked with Undergraduates (GLUE) program. Successful completion of this project will advance our understanding of the link between antibiotic resistance and nanomaterials and enable the public, regulatory agencies, and industry to make informed decisions about the use of products containing nanomaterials to protect human health. The twin problems of antibiotic resistance and the safety of engineered nanomaterials are issues of global concern. This research project will assess whether metal and metal-oxide engineered nanomaterials stimulate antibiotic resistance in bacteria. This objective will be achieved by studying the expression of antibiotic stress genes and mutative antibiotic resistance due to hereditable genetic changes in Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli in the presence of metal and metal-oxide engineered nanomaterials. The specific objectives of the work are to: i) determine sub-lethal concentrations of metal and metal-oxide nanomaterials and their associated dissolved metals for planktonic bacteria; ii) assess the occurrence and mechanistic basis for adaptive resistance in planktonic bacteria exposed to sub-lethal nanomaterial or dissolved metal concentrations; iii) evaluate the temporal transcriptional response of planktonic bacteria to sub-lethal nanomaterial or dissolved metal exposures; iv) assess mutative resistance in planktonic bacteria due to sub-lethal nanomaterial or dissolved metal exposures; and v) explore adaptive resistance in biofilms due to sub-lethal nanomaterial or dissolved metal exposures. Importantly, this project will differentiate between the impact of "intact" nanomaterials and that of dissolved metals on antibiotic resistance development.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.