Liao Zedong, Lin Keshan, Liao Weijiang, Xie Ying, Yu Guoqing, Shao Yan, Dai Min, Sun Fenghui
School of Laboratory Medicine, Chengdu Medical College, Chengdu, Sichuan, China.
Sichuan Provincial Engineering Laboratory for Prevention and Control Technology of Veterinary Drug Residue in Animal-origin Food, Chengdu Medical College, Chengdu, Sichuan, China.
Front Microbiol. 2023 May 12;14:1171339. doi: 10.3389/fmicb.2023.1171339. eCollection 2023.
The emergence of multi-drug resistant () has posed a challenging clinical problem for treating its infection. The development of novel or new antibacterial agents becomes one of the useful methods to solve this problem, and has received more attention over the past decade. Citral is reported to have antibacterial activity against , but its mechanism is yet entirely clear.
To reveal the antibacterial mechanism of citral against , comparative transcriptomic analysis was carried out to analyze the gene expression differences between the citral-treated and untreated groups. The changes of protein, adenosine triphosphate (ATP) and reactive oxygen species (ROS) content in caused by citral were also examined.
Six hundred and fifty-nine differentially expressed genes were obtained according to the comparative transcriptomic analysis, including 287 up-regulated genes and 372 down-regulated genes. The oxidoreductase activity and fatty acid degradation pathway were enriched in up-regulated genes, and ribosome and infection pathway were enriched in down-regulated genes. Meanwhile, physiological trials revealed a decline in ATP and protein levels, but an increase in ROS content within the citral-treated group. Thus, it can be inferred that the antibacterial effects of citral against were likely due to its ability to decrease ATP content by down-regulating ATP synthase genes ( and ), reduce protein content, induce cell membrane and cell wall damages, accumulate ROS, and down-regulate virulence factor genes to reduce pathogenicity.
These findings revealed the antibacterial mechanism of citral was likely a type of multi-target mode that affected multiple molecular processes in , which lays the groundwork for further exploitation of citral as a therapeutic candidate against infections.
多重耐药菌的出现给其感染的治疗带来了具有挑战性的临床问题。开发新型抗菌药物成为解决这一问题的有效方法之一，并且在过去十年中受到了更多关注。据报道，柠檬醛对多重耐药菌具有抗菌活性，但其作用机制尚不完全清楚。
为揭示柠檬醛对多重耐药菌的抗菌机制，进行了比较转录组分析，以分析柠檬醛处理组和未处理组之间的基因表达差异。还检测了柠檬醛引起的多重耐药菌中蛋白质、三磷酸腺苷（ATP）和活性氧（ROS）含量的变化。
通过比较转录组分析获得了659个差异表达基因，其中包括287个上调基因和372个下调基因。上调基因中富集了氧化还原酶活性和脂肪酸降解途径，下调基因中富集了核糖体和多重耐药菌感染途径。同时，生理学试验表明，柠檬醛处理组中的ATP和蛋白质水平下降，但ROS含量增加。因此，可以推断柠檬醛对多重耐药菌的抗菌作用可能是由于其通过下调ATP合酶基因（和）来降低ATP含量、减少蛋白质含量、诱导细胞膜和细胞壁损伤、积累ROS以及下调毒力因子基因以降低致病性的能力。
这些发现揭示了柠檬醛的抗菌机制可能是一种多靶点模式，影响了多重耐药菌中的多个分子过程，这为进一步开发柠檬醛作为抗多重耐药菌感染的治疗候选药物奠定了基础。
