Abstract
The antibiotic resistance crisis causes nearly 5 million deaths globally every year. Pseudomonas aeruginosa is a highly virulent Gram-negative bacteria that is resistant to commonly used antibiotics. Novel quaternary phosphonium compounds were highly effective against clinical isolates of P. aeruginosa compared to the widely-used disinfectant, benzalkonium chloride (BAC), marking the extent of the defensive strategy implemented by P. aeruginosa clinical isolates. The offensive strategy of P. aeruginosa of pyocyanin production showed that BAC-resistant strains of P. aeruginosa increased in pyocyanin production compared to their parent strains. Previous studies have demonstrated P. aeruginosa sensitization to Gram-positive antibiotics, which has piqued interest in the mechanism behind this phenomenon. Using a dilute growth media, P. aeruginosa was tested against a panel of Gram-positive antibiotics, with vancomycin yielding the most promising results. A significantly lower minimal inhibitory concentration of vancomycin was needed to prevent sensitized bacterial growth (16 μg/mL) than unmodified bacterial growth (>256 μg/mL). The structure of the outer membrane was investigated with N-Phenylnaphthalen-1-amine and nitrocefin. Both outer-membrane assays suggest that sensitization is not the result of a permeabilized outer membrane. In addition, divalent cation supplementation in the minimal media was done to further affirm that sensitization is not due to a permeabilized outer membrane. Additional assays such as growth inhibition over time, swimming motility, and carbon source supplementation were monitored to further explore the vancomycin mechanism of action on sensitized P. aeruginosa. Therefore, P. aeruginosa is sensitized to vancomycin through an alternate mechanism. Further experimentation with multidrug-resistant clinical isolates was conducted to explore the implications of P. aeruginosa sensitization. Future directions include seeking transient changes through RNA sequencing of the sensitized P. aeruginosa.
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