State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China.
Hubei Biopesticide Engineering Research Centre, Wuhan, Hubei, China.
Appl Environ Microbiol. 2021 Apr 27;87(10). doi: 10.1128/AEM.03165-20.
Streptococcal toxic shock-like syndrome (STSLS) caused by the epidemic strain of leads to severe inflammation and high mortality. The life and health of humans and animals are also threatened by the increasingly severe antimicrobial resistance in There is an urgent need to discover novel strategies for the treatment of infection. Suilysin (SLY) is considered to be an important virulence factor in the pathogenesis of In this study, ellipticine hydrochloride (EH) was reported as a compound that antagonizes the hemolytic activity of SLY. , EH was found to effectively inhibit SLY-mediated hemolytic activity. Furthermore, EH had a strong affinity for SLY, thereby directly binding to SLY to interfere with the hemolytic activity. Meanwhile, it was worth noting that EH was also found to have a significant antibacterial activity. , compared with traditional ampicillin, EH not only significantly improved the survival rate of mice infected with 2 strain Sc19 but also relieved lung pathological damage. Furthermore, EH effectively decreased the levels of inflammatory cytokines (interleukin-6 [IL-6], tumor necrosis factor alpha [TNF-α]) and blood biochemistry enzymes (alanine transaminase [ALT], aspartate transaminase [AST], creatine kinase [CK]) in Sc19-infected mice. Additionally, EH markedly reduced the bacterial load of tissues in Sc19-infected mice. In conclusion, our findings suggest that EH can be a potential compound for treating infection in view of its antibacterial and antihemolysin activity. In recent years, the inappropriate use of antibiotics has unnecessarily caused the continuous emergence of resistant bacteria. The antimicrobial resistance of has also become an increasingly serious problem. Targeting virulence can reduce the selective pressure of bacteria on antibiotics, thereby alleviating the development of bacterial resistance to a certain extent. Meanwhile, the excessive inflammatory response caused by infection is considered the primary cause of acute death. Here, we found that ellipticine hydrochloride (EH) exhibited effective antibacterial and antihemolysin activities against , compared with ampicillin, EH had a significant protective effect on serotype 2 strain Sc19-infected mice. Our results indicated that EH, with dual antibacterial and antivirulence effects, will contribute to treating infections and alleviating the antimicrobial resistance of to a certain extent. More importantly, EH may develop into a promising drug for the prevention of acute death caused by excessive inflammation.
链球菌中毒性休克样综合征(STSLS)由流行株引起,可导致严重炎症和高死亡率。人类和动物的生命健康也受到 抗菌耐药性日益严重的威胁。因此,迫切需要发现治疗 感染的新策略。溶血素(SLY)被认为是 致病的重要毒力因子。在本研究中,盐酸椭圆醇(EH)被报道为一种拮抗 SLY 溶血活性的化合物。结果表明,EH 能有效抑制 SLY 介导的溶血活性。此外,EH 与 SLY 具有很强的亲和力,从而直接与 SLY 结合,干扰其溶血活性。同时,值得注意的是,EH 还具有很强的抗菌活性。与传统氨苄西林相比,EH 不仅显著提高了 2 型 Sc19 感染小鼠的存活率,而且缓解了肺部病理损伤。此外,EH 还能有效降低 Sc19 感染小鼠炎症细胞因子(白细胞介素-6[IL-6]、肿瘤坏死因子-α[TNF-α])和血液生化酶(丙氨酸转氨酶[ALT]、天冬氨酸转氨酶[AST]、肌酸激酶[CK])水平。此外,EH 显著降低了 Sc19 感染小鼠组织中的细菌负荷。综上所述,鉴于 EH 的抗菌和抗溶血活性,它可能是一种治疗 感染的潜在化合物。近年来,抗生素的不当使用导致耐药菌不断出现。 的抗菌耐药性也成为一个日益严重的问题。针对毒力可以降低细菌对抗生素的选择压力,从而在一定程度上缓解细菌耐药性的发展。同时, 感染引起的过度炎症反应被认为是导致急性死亡的主要原因。在这里,我们发现盐酸椭圆醇(EH)对 具有有效的抗菌和抗溶血活性,与氨苄西林相比,EH 对 2 型 Sc19 感染小鼠具有显著的保护作用。我们的结果表明,EH 具有双重抗菌和抗病毒作用,将有助于治疗 感染,并在一定程度上缓解 对抗生素的耐药性。更重要的是,EH 可能成为预防过度炎症引起的急性死亡的一种有前途的药物。