Date of Award
Honors College Thesis
Dmitri Mavrodi, Ph.D.
Pseudomonas aeruginosa is a common hospital-acquired pathogen and is often associated with high mortality rates due to the development of multidrug-resistance. Antimicrobial plant-derived (phyto-) aldehydes present a promising alternative to antibiotics due to their broad-spectrum antimicrobial activity and low propensity to trigger resistance. However, two main problems preclude the widespread application of these compounds: chemical instability and low antimicrobial efficacy. The ongoing collaboration between the Mavrodi and Patton labs at USM has recently addressed the problem of chemical instability by incorporating plant aldehydes into polymer materials called Pro-Antimicrobial Networks via Degradable Acetals (PANDAs). Thus, this study aimed to address the low antimicrobial efficacy of phytoaldehydes. The first step involved the characterization of cellular pathways targeted by 4-methoxybenzaldehyde, which is a metabolite from star anise and a key component of PANDAs. Pseudomonas aeruginosa PAO1 was subjected to transposon mutagenesis and 10,000 mutants were screened for hypersensitivity to 4-methoxybenzaldehyde. Results of the screening revealed that inactivation of the MexAB-OprM multidrug efflux pump sensitizes P. aeruginosa to phytoaldehydes. Based onthis finding, several plant-derived efflux pump inhibitors (EPIs) were tested for the capacity to improve the antimicrobial efficacy of 4-methoxybenzaldehyde. Results of this testing revealed that epigallocatechin gallate (EGCG) from green tea acted synergistically with 4-methoxybenzaldehyde and significantly reduced its minimal inhibitory concentration. Finally, the response of four medically important P. aeruginosa efflux pump genes to 4-methoxybenzaldehyde and EGCG was analyzed using RT-qPCR. The result demonstrated that the phytoaldehyde significantly upregulated MexCD-OprJ and MexEF-OprN efflux pumps and the addition of EGCG reversed this effect. Collectively, our results highlighted the importance of active efflux in the resistance of P. aeruginosa to phytoaldehydes and the potential of EPIs in improving the efficacy of these natural antimicrobials.
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Namjilsuren, Sanchirmaa, "The Importance of RND-type Efflux Pumps in the Interactions of Pseudomonas aeruginosa with 4-Methoxybenzaldehyde" (2019). Honors Theses. 639.