Evaluation of analogs of mutacin 1140 in systemic and cutaneous methicillin-resistant Staphylococcus aureus infection models in mice.
Evaluation of analogs of mutacin 1140 in systemic and cutaneous methicillin-resistant Staphylococcus aureus infection models in mice.
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DOI：
10.3389/fmicb.2022.1067410
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发表时间：
2022
影响因子：
5.2
通讯作者：
Smith, Leif
中科院分区：
文献类型：
--
作者：
Ju, Min;Joseph, Thushinari;Hansanant, Nopakorn;Geng, Mengxin;Williams, McKinley;Cothrell, Andrew;Buhrow, Andrew Riley;Austin, Frank;Smith, Leif
慕达星1140(Mu1140)是一种对革兰氏阳性菌(如金黄色葡萄球菌)有效的抗生素。该抗生素由口腔细菌变形链球菌产生，是AI类抗生素表皮蛋白家族的成员。该抗生素通过与细胞壁前体脂质II结合，阻止细胞壁合成，并通过破坏细菌膜来发挥其抑制活性。在以前的研究中，与天然的Mu1140相比，新的Mu1140的K2A和R13A类似物已被确定具有更好的药代动力学特性。在这项研究中，使用Mu1140 K2A和R13A类似物的组合配方在治疗MRSA菌血症方面被证明比本地Mu1140或万古霉素更有效。这些类似物也被证明对治疗MRSA皮肤感染有效。K2A和R13A类似物的使用可能为治疗严重的革兰氏阳性细菌感染提供一种未来的替代方案。在之前的一项研究中，Mu1140类似物被证明有明显更长的药物清除时间，随着时间的推移导致更高的血浆浓度。这些特性需要进一步测试，以确定类似物是否对治疗系统性MRSA和急性皮肤感染有效。在这项研究中，Mu1140类似物被证明比目前可用的治疗全身和皮肤MRSA感染的方法更有效。此外，这项研究清楚地表明，新的类似物在治疗系统性MRSA感染方面优于本土的Mu1140。这些发现支持使用K2A和R13A-1140类似物继续药物产品开发的努力，这些类似物可能会改善严重细菌感染的结果。
Mutacin 1140 (Mu1140) is a potent antibiotic against Gram-positive bacteria, such as Staphylococcus aureus. The antibiotic is produced by the oral bacterium Streptococcus mutans and is a member of the epidermin family of type AI lantibiotics. The antibiotic exerts its inhibitory activity by binding to the cell wall precursor lipid II, blocking cell wall synthesis, and by disrupting bacterial membranes. In previous studies, the novel K2A and R13A analogs of Mu1140 have been identified to have superior pharmacokinetic properties compared to native Mu1140. In this study, the use of a combined formulation of the Mu1140 K2A and R13A analogs was shown to be more effective at treating MRSA bacteremia than the native Mu1140 or vancomycin. The analogs were also shown to be effective in treating an MRSA skin infection. The use of K2A and R13A analogs may provide a future alternative for treating serious Gram-positive bacterial infections. In a previous study, the Mu1140 analogs were shown to have significantly longer drug clearance times, leading to higher plasma concentrations over time. These properties warranted further testing to determine whether the analogs are effective for the treatment of systemic MRSA and acute skin infections. In this study, Mu1140 analogs were shown to be more effective than currently available treatments for systemic and skin MRSA infections. Further, the study clearly shows that the new analogs are superior to native Mu1140 for the treatment of a systemic MRSA infection. These findings support continued drug product development efforts using the K2A and R13A Mu1140 analogs, and that these analogs may ameliorate the outcome of serious bacterial infections.
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影响因子：
4.9
作者：
Simonetti, Oriana;Lucarini, Guendalina;Cirioni, Oscar
通讯作者：
Cirioni, Oscar
影响因子：
4.9
作者：
Geng, Mengxin;Ravichandran, Akshaya;Smith, Leif
通讯作者：
Smith, Leif
影响因子：
11.8
作者：
Finberg, RW;Moellering, RC;Rybak, MJ
通讯作者：
Rybak, MJ
影响因子：
4.4
作者：
Escano, Jerome;Ravichandran, Akshaya;Smith, Leif
通讯作者：
Smith, Leif
DOI：
10.1046/j.1432-1033.2000.01777.x
发表时间：
2000-12-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Smith, L;Novák, J;Edison, AS
通讯作者：
Edison, AS