**1. Introduction**

Antimicrobial resistance is an especially pressing problem in the clinical setting today. The pinnacle of secondary infections due to convergence between communicable disease

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(CD) and noncommunicable diseases (NCD) further complicates the problem [1]. There is a two-sided role for antibiotics; and although their uncontested and unquestionable role was recognized to significantly reduce the statistics of the infectious diseases burden worldwide, their rampant use also contributed to the unexpected emergence of antibiotic resistant microorganisms attributed to over‐prescription and misuse, hence, the emergence of the multidrug resistant Enterobacteriaceae, especially *Escherichia coli* (*E. coli*). Adversely, the last line of antibiotics, colistin, which had only been recently revived since 1959 amidst the fairly new emergence of carbapenem-resistant *Enterobacteriaceae*, had been reported by Chinese researchers to be inefficacious against *E. coli* recently, in infected pigs from a farm near Shanghai, and the spread of colistin resistance had increased significantly especially in the agriculture industry over time, which may be escalated to a global scale [2, 3]. With the establishment of new resistance, the Chinese authors have emphasized the urgent need for coordinated global action in the fight against pan‐drug‐resistant Gram‐negative bacteria and one of these strategies proposed included investigation into natural products, in this case, essential oils. This chapter aims to introduce the usage of synergistic combinatorial therapy between different classes of antibiotics and essential oils against multidrug resistant *E. coli* (MDR *E. coli*) and to detail the methodologies used to establish synergism as well as the mechanisms involved.

it's active site and rendering it inactive [7, 8]. Hence, the action of β‐lactam antibiotic halts cell wall synthesis of bacteria, which eventually compromises the rigidity of the cell wall,

Essential Oils: The Ultimate Solution to Antimicrobial Resistance in *Escherichia coli*?

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Fluoroquinolones is another class of antibiotics that exert their effect on both Gram‐positive and -negative bacteria. The main structural feature of this particular antibiotic class is the presence of the fluorine atom within these antibiotics. It exhibits a broad spectrum activity against a large panel of bacteria as this group of antibiotic inhibits DNA synthesis by locking both the DNA gyrase and topoisomerase IV with the DNA strand during DNA replication. This prevents the action of other enzymes such as the RNA polymerase and DNA helicase for normal DNA replication, which eventually leads to cell death [9, 10]. Commonly prescribed fluoroquinolones include ciprofloxacin, gemifloxacin, levofloxacin, and moxifloxacin, which

Aminoglycoside is another major group of antibiotics showing enhanced potency toward Gram-negative bacteria. As the name suggests, this compound comprises of sugar units bounded to an amino group. Aminoglycosides exhibit high potency as well as a broad spectrum of action as it disrupts protein synthesis by binding only to the prokaryotic 30S ribosomal subunit, which then impairs the proofreading mechanism during protein translation [11, 12]. This disruption produces dysfunctional proteins, either due to misreading or premature termination, and eventually causes cell death. Even though aminoglycosides are specific toward prokaryotic ribosome, toxicity had been observed and reported in mammalian cells when a high dosage was applied [13]. Hence, aminoglycosides are only prescribed during life-threatening infections. Commonly prescribed aminoglycosides includes amika-

Nitrofurans are a highly potent antibiotic class, which contain a furan ring and a nitro group. They are only used against urinary tract infections, especially when the infection is caused by an antibiotic-resistant pathogen. This is due to the high metabolism rate of the liver in partially breaking down the ingested nitrofuran. The remaining nitrofuran is then concentrated in the urinary bladder and thus suitable to be used in urinary tract infection, enabling targeted delivery [14]. High potency of nitrofuran is contributed by its diverse mode of actions when used against bacteria. In the presence of bacterial nitroreductases, nitrofuran is converted into reactive intermediates such as peroxynitrite and nitric oxide, which attack the bacterial ribosome, thus halting the protein synthesis in bacteria [15]. It was also reported that these reactive intermediates of nitrofuran can attack bacterial DNA as well as acting as a quorum sensing inhibitor [16, 17]. Due to the attribute of their multiple‐action mode, resistance toward nitrofurans

leading to cell lysis.

*2.1.2. Fluoroquinolone*

*2.1.3. Aminoglycosides*

had relatively low adverse effects.

cin, gentamicin, and streptomycin.

*2.1.4. Nitrofurans*
