Minami Masaaki, Ando Takafumi, Hashikawa Shin-Nosuke, Torii Keizo, Hasegawa Tadao, Israel Dawn A, Ina Kenji, Kusugami Kazuo, Goto Hidemi, Ohta Michio
Department of Therapeutic Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
Antimicrob Agents Chemother. 2004 Oct;48(10):3782-8. doi: 10.1128/AAC.48.10.3782-3788.2004.
Glycine is the simplest amino acid and is used as a metabolic product in some bacteria. However, an excess of glycine inhibits the growth of many bacteria, and it is used as a nonspecific antiseptic agent due to its low level of toxicity in animals. The effect of glycine on Helicobacter pylori is not precisely known. The present study was conducted to investigate (i) the effect of glycine on clarithromycin (CLR)-resistant and -susceptible strains of H. pylori, (ii) the effect of glycine in combination with amoxicillin (AMX), and (iii) the postantibiotic effect (PAE). The MIC at which 90% of strains are inhibited for glycine was almost 2.5 mg/ml for 31 strains of H. pylori, including CLR-resistant strains. We constructed isogenic CLR-resistant mutant strains by natural transformation and investigated the difference between clinical wild-type strains and isogenic mutants. There were no differences in the MICs between CLR-resistant and -susceptible strains or between clinical wild-type and mutant strains. The combination of AMX and glycine showed synergistic activity, with the minimum bactericidal concentration of AMX with glycine decreasing to 1/10 that of AMX alone. Glycine showed no PAE against H. pylori. These results suggest that glycine may be a useful antimicrobial agent against H. pylori not only alone but also in combination with antibacterial drugs for the treatment of H. pylori-associated diseases. Glycine may represent a component of a new type of eradication therapy for CLR-resistant H. pylori.
甘氨酸是最简单的氨基酸,在一些细菌中用作代谢产物。然而,过量的甘氨酸会抑制许多细菌的生长,并且由于其在动物体内的低毒性水平,它被用作非特异性防腐剂。甘氨酸对幽门螺杆菌的作用尚不完全清楚。本研究旨在调查:(i)甘氨酸对克拉霉素(CLR)耐药和敏感的幽门螺杆菌菌株的影响;(ii)甘氨酸与阿莫西林(AMX)联合使用的效果;(iii)抗生素后效应(PAE)。对于31株幽门螺杆菌(包括CLR耐药菌株),90%菌株被抑制时甘氨酸的最低抑菌浓度(MIC)几乎为2.5mg/ml。我们通过自然转化构建了同基因CLR耐药突变株,并研究了临床野生型菌株与同基因突变株之间的差异。CLR耐药和敏感菌株之间或临床野生型和突变株之间的MIC没有差异。AMX与甘氨酸联合显示出协同活性,AMX与甘氨酸联合的最低杀菌浓度降至单独使用AMX时的1/10。甘氨酸对幽门螺杆菌没有PAE。这些结果表明,甘氨酸不仅单独使用,而且与抗菌药物联合使用时,可能是一种治疗幽门螺杆菌相关疾病的有用抗菌剂。甘氨酸可能代表一种新型的CLR耐药幽门螺杆菌根除疗法的组成部分。