Characterizing the Evolutionary Behavior of Bacteria in the Presence of Iron Nanoparticles.

点击翻译按钮获取中文摘要

Graves1602593The spread of multidrug resistant bacteria is now a crucial concern for modern society. For example in 2012, methicillin resistant Staphylococcus aureus (MRSA) killed more people in the USA than AIDS, hepatitis B, and tuberculosis combined. To address this concern there is a need for novel antimicrobial treatments. One of the most promising of these is the use of metallic/metallic oxide nanoparticles. However, many researchers in this field have not considered the possibility that bacteria can evolve resistance to metals and metallic oxides (silver, copper, iron) as quickly as they did to traditional antibiotics. This research project will specifically study the methodology, speed, and mechanism by which bacterium can evolve resistance to iron/iron oxide nanoparticles. To examine how resistance to iron toxicity may arise in bacteria, the PI proposes to utilize a series of laboratory experiments with genomic resequencing. This knowledge will provide science-based data for more appropriate use of these antimicrobials so that the development of resistance is avoided or minimized. To examine how bacteria may evolve resistance to iron/iron oxide nanoparticles the PI will use laboratory experiments to produce iron resistant strains of E. coli K-12 MG1655 via exposure to ?×-Fe2O3 (maghemite) and Fe3O4 (magnetite) nanoparticles. The PI will utilize different ancestral strains to derive into the two different types of iron resistant populations. One of the ancestors will have no prior metal resistance and the second ancestor will have a history of silver resistance. The PI will use whole genome resequencing to examine the genomes of the ancestors and the iron-resistant derived populations. This will allow the PI to test whether previously existing heavy metal resistance mechanisms provide an advantage in the development of resistance to magnetic iron oxide. These experiments will also allow the PI to test whether the genomic adaptations to ferrous iron (Fe2+) are different from those adaptations engendered by ferric iron (Fe3+) toxicity. This project will provide crucial genomic-based information concerning the mechanisms by which bacteria evolve resistance to metal/metallic oxide nanoparticles. The resulting data will be useful for researchers developing nano-based interventions to control multi-drug resistant bacteria. The ability to control the development of resistance will improve the sustainability of potential medical uses of metallic/metallic oxide nanoparticles. This research could benefit both the scientific community in general by elucidating mechanisms of bacteria resistance and the general public by the reduction in infectious disease. This research will be conducted at the Joint School of Nanosciences and Nanoengineering through a partnership between North Carolina A &T State University (HBCU) and the University of North Carolina (UNC) Greensboro (a minority-serving institution). This project will also involve encouraging and mentoring underrepresented and first-generation college students in science and engineering disciplines