Phenolic Compound Ethyl 3,4-Dihydroxybenzoate Retards Drug Efflux and Potentiates Antibiotic Activity.

The World Health Organization indicated that antibiotic resistance is one of the greatest threats to health, food security, and development in the world. Drug resistance efflux pumps are essential for antibiotic resistance in bacteria. Here, we evaluated the plant phenolic compound ethyl 3,4-dihydroxybenzoate (EDHB) for its efflux pump inhibitory (EPI) activity against drug-resistant Escherichia coli. The half-maximal inhibitory concentration, modulation assays, and time-kill studies indicated that EDHB has limited antibacterial activity but can potentiate the activity of antibiotics for drug-resistant E. coli. Dye accumulation/efflux and MALDI-TOF studies showed that EDHB not only significantly increases dye accumulation and reduces dye efflux but also increases the extracellular amount of antibiotics in the drug-resistant E. coli, indicating its interference with substrate translocation via a bacterial efflux pump. Molecular docking analysis using AutoDock Vina indicated that EDHB putatively posed within the distal binding pocket of AcrB and in close interaction with the residues by H-bonds and hydrophobic contacts. Additionally, EDHB showed an elevated postantibiotic effect on drug-resistant E. coli. Our toxicity assays showed that EDHB did not change the bacterial membrane permeability and exhibited mild human cell toxicity. In summary, these findings indicate that EDHB could serve as a potential EPI for drug-resistant E. coli.

Identified Seaweed Compound Diphenylmethane Serves as an Efflux Pump Inhibitor in Drug-Resistant Escherichia coli.

Drug efflux pumps are one of the major elements used by antibiotic-resistant bacteria. Efflux pump inhibitors (EPIs) are potential therapeutic agents for adjunctive therapy, which can restore the activity of antibiotics that are no longer effective against pathogens. This study evaluated the seaweed compound diphenylmethane (DPM) for its EPI activity. The IC50 and modulation results showed that DPM has no antibacterial activity but can potentiate the activity of antibiotics against drug-resistant E. coli. Time-kill studies reported that a combination of DPM and erythromycin exhibited greater inhibitory activity against drug-resistant Escherichia coli. Dye accumulation and dye efflux studies using Hoechst 33342 and ethidium bromide showed that the addition of DPM significantly increased dye accumulation and reduced dye efflux in drug-resistant E. coli, suggesting its interference with dye translocation by an efflux pump. Using MALDI-TOF, it was observed that the addition of DPM could continuously reduce antibiotic efflux in drug-resistant E. coli. Additionally, DPM did not seem to damage the E. coli membranes, and the cell toxicity test showed that it features mild human-cell toxicity. In conclusion, these findings showed that DPM could serve as a potential EPI for drug-resistant E. coli.

Using ambient mass spectrometry to explore the origins of phthalate contamination in a mass spectrometry laboratory.

Phthalates are known endocrine disruptors that can have adverse effects on human hormonal balance and development. Phthalates are semi-volatile chemical compounds, thus they can continuously leach from phthalate-containing objects and pollute the environments such as offices or laboratories, where workers in these spaces can inhale potentially harmful amounts of phthalates. Identifying and removing phthalate-contaminated objects from these indoor environments can effectively eliminate exposure to these environmental hormones. However, as of now, it is highly impractical to perform a large-scale screening of phthalate-containing objects using conventional analytical techniques which are usually time- and labor-intensive. In this study, thermal desorption electrospray ionization mass spectrometry (TD-ESI/MS) combined with probe sampling was used to screen phthalates on all non-metallic objects in a mass spectrometry (MS) laboratory. Due to sample pre-treatment was unnecessary and there was no limitation of sampling on sample's shape, size, and material, screening of phthalates on an object using this ambient mass spectrometric approach was completed within 30 s, which enable sufficient and high-throughput screening. Phthalate signals of di(2-ethylhexyl)phthalate (DEHP), diisononyl phthalate (DINP) and diisodecyl phthalate (DIDP) were qualitatively detected on the surfaces of the filters of air conditioners and air purifiers and laboratory door, indicating there was a possibility of phthalates contamination in the studying area. Other screened objects in the laboratory included the ceiling, wall, floor, chairs, benches, pipes, mechanical vacuum pump tubes, and some personal belongings, all of which contained phthalates. Among them, floor and mechanical vacuum pump tubes contained high concentration of DEHP, DINP and DIDP, suggesting they were the main sources of phthalate contamination in the MS laboratory.