Synergistic Activity of Equol and Meropenem against Carbapenem-Resistant Escherichia coli

Abstract

The emergence of carbapenem-resistant Enterobacterales (CRE) seriously limits treatment options for bacterial infections. Combined drugs are an effective strategy to treat these resistant strains. This study aimed to evaluate the synergistic effect of equol and meropenem against carbapenem-resistant Escherichia coli. First, this study investigated the antibacterial activity of carbapenems on clinically isolated E. coli strains by analyzing the minimum inhibitory concentrations (MICs). The E. coli strains were all resistant to carbapenem antibiotics. Therefore, we confirmed the cause of carbapenem resistance by detecting blaKPC and blaOXA-48 among the carbapenemase genes using polymerase chain reaction (PCR) analysis. Checkerboard and time-kill analyses confirmed that equol restored the susceptibility of carbapenem-resistant E. coli to meropenem. Also, the transcription levels of specific carbapenemase genes in E. coli were significantly suppressed by equol. The study also evaluated the anti-virulence effects of equol on bacterial biofilm and motility through phenotypic and genotypic analyses. In conclusion, our results revealed that equol had a synergistic effect with meropenem on carbapenem-resistant E. coli. Therefore, this study suggests that equol is a promising antibiotic adjuvant that prevents the expression of carbapenemases and virulence factors in carbapenem-resistant E. coli.

Fingolimod Promotes Antibacterial Effect of Doripenem against Carbapenem-Resistant Escherichia coli

“…In particular, resistance to carbapenem antibiotics used as the last line of defense against Enterobacteriaceae infections is a worldwide problem [ 17 ]. Recently, there has been growing interest in finding synergistic adjuvants that can solve the problem of MDR [ 6 ]. To deter the emergence and spread of antibiotic-resistant bacteria, antibacterial research to identify new antibiotic adjuvants is considered urgent.…”

“…However, sometimes, E. coli causes diseases such as cystitis, urinary tract infections, appendicitis, peritonitis, and pneumonia [ 3 , 4 , 5 ]. Recent data show rapidly increasing rates of infections by multidrug-resistant (MDR) gram-negative bacilli due to their resistance to carbapenems, resulting in high morbidity and mortality [ 6 ].…”

Auranofin promotes antibacterial effect of doripenem against carbapenem-resistant Acinetobacter baumannii

“…The gene transcripts were quantified using TOPreal™ qPCR 2X PreMIX (Enzynomics, Dajeon, Korea) and a StepOnePlus Real‐Time PCR System (Applied Biosystems, Foster City, CA, USA). The qPCR conditions were described in a previous study (Kim & Eom, 2021b). Oligonucleotides and annealing temperatures for each primer are listed in Table 1.…”

“…The quantity and purity of the extracted DNA were assessed using a BioDrop μLITE (BioDrop Ltd., Cambridge, UK). The PCR was then performed as described before (Kim & Eom, 2021b). Oligonucleotides and annealing temperatures for each primer are listed in Table 1.…”

“…The treated bacterial cells were incubated at 37°C for 24 h. To investigate the eradicative effect of auranofin on mature biofilms, overnight cultures adjusted to a density of 1 × 10 6 CFU per ml were incubated at 37°C for 24 h, followed by removal of planktonic cells and washing with phosphate-buffered saline (PBS). The remaining adherent cells were treated with various concentrations of auranofin (8 to 64 μg ml −1 ) and further incubated at 37°C for 24 h. Biofilms exposed to auranofin were quantified using the crystal violet assay as previously described (Kim & Eom, 2021b). Total biofilm biomass was analysed at 595 nm.…”