Abstract

The objective of this study was to evaluate the antibacterial mechanisms of phenolic acids as natural approaches against multi-drug resistant Escherichia coli (E. coli). For that purpose, five phenolic acids were combined with each other and 31 combinations were obtained in total. To select the most potent and effective combination, all of the obtained combinations were examined for minimum inhibitory concentration (MIC) and it was found that the compound phenolic acid (CPA) 19 (protocatechuic acid, hydrocinnamic acid, and chlorogenic acid at concentrations of 0.833, 0.208, and 1.677 mg/mL, respectively) showed better efficacy against E. coli compared to other combinations. Furthermore, based on tandem mass tag (TMT) proteomics, the treatment of CPA 19 significantly downregulated the proteins associated with resistance (Tsr, Tar, CheA, and CheW), OmpF, and FliC of multidrug-resistant E. coli. At the same time, we proved that CPA 19 improves the sensitivity of E. coli to antibiotics (ceftriaxone sodium, amoxicillin, fosfomycin, sulfamonomethoxine, gatifloxacin, lincomycin, florfenicol, cefotaxime sodium, and rifampicin), causes the flagellum to fall off, breaks the structure of the cell wall and cell membrane, and leads to macromolecules leaks from the cell. This evidence elaborated the potential therapeutic efficacy of CPA 19 and provided a significant contribution to the discovery of antibacterial agents.

Highlights

  • About 78 years ago, penicillin and other antibiotics were discovered as antimicrobial agents and introduced in various clinical treatments because of their positive influences in preventing bacterial infections (Paitan, 2018)

  • After the treatment of compound phenolic acid (CPA) 19 with 1/2 minimum inhibitory concentration (MIC), significant changes were observed in the bacterial cell wall, the surface area of the cell wall became rough and the boundary between the cell wall and cell membrane became fuzzy, in addition, there was no flagellum on the surface of the bacterial cell (Figure 10B)

  • Our results of the MICs revealed the antibacterial effects of each CPA

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Summary

Introduction

About 78 years ago, penicillin and other antibiotics were discovered as antimicrobial agents and introduced in various clinical treatments because of their positive influences in preventing bacterial infections (Paitan, 2018). Abraham and Chain (1988) reported the emergence of antimicrobial resistance. The resistance genes of the seven E. coli strains are shown in Table 1 (identification by the 25 μL PCR reaction system). Among these resistant bacterial strains, species of E. coli have emerged against the variety of antibiotic agents used in clinical practice, which damages the production of the animal industry, and seriously affects the health of human beings.

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