## 4 Conclusions  
From our genomic transcriptomics data, eugenol was shown to affect targets/pathways that are involved in amino acid metabolism and protein translation, both of which are essential for development and transcriptional processes in the survival of bacteria. The functional roles and mechanisms of these target genes are present in both Gram-positive and Gram-negative bacteria. Eugenol has a high level of penetrability into the bacterial periplasm and cytoplasm, mechanistically enabled through the disruption of the cell wall and complex matrices of the cytoplasm. Although the in-depth understanding of the physicochemical properties of eugenol's entry into MRSA is limited, the structure-activity relationship should be explored through high-throughput screening (HTS) and molecular docking to further our understanding of the molecular mechanism. The emergence of and continuous increase in bacterial resistance to antibacterial agents is currently a global challenge. Eugenol may be used in combination with currently available antibacterial agents as combination therapy to address this global pandemic of bacterial resistance. Antibiotics such as methicillin, vancomycin, and teicoplanin are known to disrupt the peptidoglycan complex, and can be used in combination with other antibacterial agents to achieve multiple-target efficiency, thereby improving their antibacterial activity. An example in this case is the study conducted on the combinatory effect of betulinaldehyde with methicillin, which reduces the minimum inhibitory concentrations (MICs) in MSSA [27]. In particular, combining eugenol with broad-spectrum inhibitors of _argC_ or downstream genes, or inhibitors of protein synthesis, polyamine synthesis, alarmone ((p)ppGpp) synthesis, or the bacterial stringent response, may yield summative/synergistic effects. Interestingly, [PERSON] et al. [28] provided a comprehensive review of bacterial biofilm antagonists that could be administered with eugenol as a combination drug therapy. The wide array of molecules discussed as potential and proven biofilm antagonists includes bromoagelfierin, oroidin, 2-aminoimidazole derivatives, benzimidazole analogues, indole-triazole-amide analogues, resveratrol and its oligomers, diphenyl disulphide, \(S\)-phenyl-l-cysteine sulfoxide, ajoene, brominated furanone analogues, bromopyrrole alkaloids, skylamycins, cembranoids, synthetic \(N\)-acyl homoserine lactone analogues, and carolacton. With the latter extensive array of molecules in our arsenal, which could potentiate the action of eugenol, we predict that the current subinhibitory concentration of eugenol against MRSA (0.0012 mg/mL) can be significantly reduced. This work describes the first genome-wide transcriptional analysis of upregulated and downregulated genes in MRSA in response to eugenol, utilising a whole-genome microarray. The global transcriptomic profile of eugenol-treated MRSA shows fluctuations of genes involved in cysteine and methionine metabolism, as well as arginine and proline metabolism, as validated by qPCR. These genes that fluctuated in expression upon challenge with eugenol are important for the survival of MRSA, and show promise as novel targets for antibacterial drug design and development. Further research into the potential combinatory/synergistic effects of eugenol with _luxS_ inducers and _argC_ inhibitors will better facilitate our understanding of the response of both genes under stringent conditions. [PERSON] and [PERSON] conceptualised and designed the study. [PERSON] and [PERSON] collected the samples, and performed the treatment and RNA extraction. [PERSON], [PERSON], [PERSON] and [PERSON] analysed the microarray results. [PERSON] drafted the manuscript, with input from [PERSON], [PERSON] and [PERSON]. All authors have read, commented on, and approved the final manuscript. All authors have read and agreed to the published version of the manuscript.