The physicochemical features that affect cell-membrane permeability of bacteria are currently not well understood. Due to the lack of tools to predict penetration of the bacterial envelope, the discovery and development of novel antibiotics is at a standstill. For this reason, the increasing spread of resistant bacteria has become a major threat to public health because these pathogens remain unchallenged. To understand how intrinsic properties, such as porins and efflux pumps, of Gram-negative bacteria influence membrane permeability and consequently, antibiotic uptake, we have developed a systematic approach to evaluate the penetration of various compounds into several strains of Escherichia coli. We study Wild Type, a porin (ompR) knockout, and an efflux pump (tolC) knockout to measure the effects that these physicochemcial properties have on antibacterial uptake. Minimum inhibitory concentrations are calculated for eighteen different compounds when tested against these three strains of E. coli. Next, compound accumulation is assessed through LC-MS/MS analysis and killing kinetics are observed. Through this, a relationship between chemical structure and bacterial membrane permeability can be identified, thus a better understanding of the roles of porins and efflux pumps in the development of antimicrobial resistance is gained.
| Identifer | oai:union.ndltd.org:CLAREMONT/oai:scholarship.claremont.edu:cmc_theses-2590 |
| Date | 01 January 2017 |
| Creators | Munoz, Kristen |
| Publisher | Scholarship @ Claremont |
| Source Sets | Claremont Colleges |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | CMC Senior Theses |
| Rights | © 2016 Kristen A Munoz |
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