Feng Miao, Yi Xiaoyu, Feng Yanling, He Feng, Xiao Zonghui, Yao Hailan
Department of Biochemistry and Immunology, Capital Institute of Pediatrics, Beijing, 100020, China.
Capital Institute of Pediatrics, Beijing, 100020, China.
Heliyon. 2024 Jul 26;10(15):e35326. doi: 10.1016/j.heliyon.2024.e35326. eCollection 2024 Aug 15.
ococcus aureus (), a prevalent human pathogen known for its propensity to cause severe infections, has exhibited a growing resistance to antibiotics. Lysine acetylation (Kac) is a dynamic and reversible protein post-translational modification (PTM), played important roles in various physiological functions. Recent studies have shed light on the involvement of Kac modification in bacterial antibiotic resistance. However, the precise relationship between Kac modification and antibiotic resistance in remains inadequately comprehended.
We compared the differential expression of acetylated proteins between erythromycin-resistant (Ery-R) and erythromycin-susceptible (Ery-S) strains of by 4D label-free quantitative proteomics technology. Additionally, we employed motif analysis, functional annotation and PPI network to investigate the acetylome landscape and heterogeneity of . Furthermore, polysome profiling experiments were performed to assess the translational status of ribosome.
6791 Kac sites were identified on 1808 proteins in , among which 1907 sites in 483 proteins were quantified. A total of 548 Kac sites on 316 acetylated proteins were differentially expressed by erythromycin pressure. The differentially acetylated proteins were primarily enriched in ribosome assembly, glycolysis and lysine biosynthesis. Bioinformatic analyses implied that Kac modification of ribosomal proteins may play an important role in erythromycin resistance of Western bolt and polysome profiling experiments indicated that the increased Kac levels of ribosomal proteins in the resistant strain may partially offset the inhibitory effect of erythromycin on ribosome function.
Our findings confirm that Kac modification is related to erythromycin resistance in and emphasize the potential roles of ribosomal proteins. These results expand our current knowledge of antibiotic resistance mechanisms, potentially guiding future research on PTM-mediated antibiotic resistance.
金黄色葡萄球菌是一种常见的人类病原体，以其易于引起严重感染而闻名，并且已表现出对抗生素的耐药性不断增强。赖氨酸乙酰化（Kac）是一种动态且可逆的蛋白质翻译后修饰（PTM），在各种生理功能中发挥重要作用。最近的研究揭示了Kac修饰与细菌抗生素耐药性有关。然而，金黄色葡萄球菌中Kac修饰与抗生素耐药性之间的确切关系仍未得到充分理解。
我们通过4D无标记定量蛋白质组学技术比较了金黄色葡萄球菌红霉素耐药（Ery-R）菌株和红霉素敏感（Ery-S）菌株之间乙酰化蛋白质的差异表达。此外，我们采用基序分析、功能注释和蛋白质-蛋白质相互作用（PPI）网络来研究金黄色葡萄球菌的乙酰化蛋白质组图谱和异质性。此外，进行了多核糖体分析实验以评估核糖体的翻译状态。
在金黄色葡萄球菌的1808种蛋白质上鉴定出6791个Kac位点，其中483种蛋白质上的1907个位点被定量。在红霉素压力下，316种乙酰化蛋白质上共有548个Kac位点差异表达。差异乙酰化蛋白质主要富集在核糖体组装、糖酵解和赖氨酸生物合成中。生物信息学分析表明，核糖体蛋白的Kac修饰可能在金黄色葡萄球菌对红霉素的耐药性中起重要作用。蛋白质免疫印迹和多核糖体分析实验表明，耐药菌株中核糖体蛋白的Kac水平升高可能部分抵消红霉素对核糖体功能的抑制作用。
我们的研究结果证实Kac修饰与金黄色葡萄球菌对红霉素的耐药性有关，并强调了核糖体蛋白的潜在作用。这些结果扩展了我们目前对抗生素耐药机制的认识，可能为未来PTM介导的抗生素耐药性研究提供指导。
