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The misuse of antibiotics has resulted in the emergence of many antibiotic-resistant strains which seriously threaten human health. Protein post-translational modifications, especially acetylation, tightly control bacterial metabolism.

Fibroblast growth factor (FGF) 8b interacts with its receptors and promotes angiogenesis in hormone‑dependent tumors. In the present study, we demonstrated that a short peptide, termed 8b‑13, which mimics part of the FGF8b structure, significantly inhibited the proliferation and migration of human umbilical vein endothelial cells (HUVECs) triggered by FGF8b using 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide (MTT), flow cytometry and an in vitro scratch assay. In addition, the findings from western blotting and reverse transcription‑quantitative polymerase chain reaction revealed that 8b‑13 appeared to counteract the effects of FGF8b on the expression of cyclin D1, the activation of signaling cascades, and the expression of proangiogenic factors; these actions may be involved in the mechanism underlying the inhibitory effects of 8b‑13 on FGF8b‑induced HUVEC proliferation and migration. The present results suggested that 8b‑13 may be considered a potent FGF8b antagonist with antiangiogenic activity, and may have potential as a novel therapeutic agent for the treatment of cancer characterized by abnormal FGF8b upregulation.

Antibiotic resistance is increasingly becoming a serious challenge to public health. The regulation of metabolism by post-translational modifications (PTMs) has been widely studied; however, the comprehensive mechanism underlying the regulation of acetylation in bacterial resistance against antibiotics is unknown. Herein, with Escherichia coli as the model, we performed quantitative analysis of the acetylated proteome of wild-type sensitive strain (WT) and ampicillin- (Re-Amp), kanamycin- (Re-Kan), and polymyxin B-resistant (Re-Pol) strains. Based on bioinformatics analysis combined with biochemical validations, we found that a common regulatory mechanism exists between the different resistant strains. Acetylation negatively regulates bacterial metabolism to maintain antibiotic resistance, but positively regulates bacterial motility. Further analyses revealed that key enzymes in various metabolic pathways were differentially acetylated. Particularly, pyruvate kinase (PykF), a key glycolytic enzyme regulating bacterial metabolism, and its acetylated form were highly expressed in the three resistant types and were identified as reversibly acetylated by the deacetylase CobB and the acetyl-transferase PatZ, and also could be acetylated by non-enzyme AcP in vitro. Further, the deacetylation of Lys413 of PykF increased the enzyme activity by changing the conformation of ATP binding site of PykF, resulting in an increase in energy production, which in turn increased the sensitivity of drug-resistant strains to antibiotics. This study provides novel insights for understanding bacterial resistance and lays the foundation for future research on regulation of acetylation in antibiotic-resistant strains.ImportanceThe misuse of antibiotics has resulted in an emergence of a large number of antibiotic-resistant strains, which seriously threaten human health. Bacterial metabolism is tightly controlled by protein post-translational modifications, especially acetylation. However, the comprehensive mechanism underlying regulation of acetylation in bacterial resistance remains unexplored. Here, acetylation was found to positively regulate bacterial motility and negatively regulate energy metabolism, which was common in all the different antibiotic-resistant strains. Moreover, the acetylation and deacetylation process of PykF was uncovered, and deacetylation of the Lys 413 of PykF was found to contribute to bacterial sensitivity to antibiotics. This study provides a new direction for research on development of bacterial resistance through post-translational modifications and provides a theoretical basis for the development of antibacterial drugs.