Petschow B W, Batema R P, Ford L L
Mead Johnson Research Center, Bristol-Myers Squibb Co., Evansville, Indiana 47721, USA.
Antimicrob Agents Chemother. 1996 Feb;40(2):302-6. doi: 10.1128/AAC.40.2.302.
Previous studies have shown that various short- and medium-chain free fatty acids (FFAs) and their corresponding monoacylglycerol esters (MGs) have antibacterial activity in vitro against primarily gram-positive bacteria. More recent studies have also shown that the growth of Helicobacter spp. is inhibited by linoleic acid and arachidonic acid. The purpose of the present study was to evaluate the susceptibility of Helicobacter pylori to the in vitro bactericidal properties of medium-chain MGs and FFAs. Incubation of H. pylori with saturated MGs, ranging in carbon chain length from C10:0 to C14:0, at 1 mM caused a 4-log-unit or greater reduction in the number of viable bacteria after exposure for 1 h. Lower levels of bactericidal activity were observed with C9:0, C15:0, and C16:0 MGs. In contrast, lauric acid (C12:0) was the only medium-chain saturated FFA with bactericidal activity against H. pylori. The MGs and FFAs were bactericidal after incubation for as little as 15 min at neutral or acidic pHs. Higher levels of MGs and FFAs were required for bactericidal activity in the presence of higher amounts of protein in liquid diets. We also found that the frequency of spontaneous development of resistance by H. pylori was higher for metronidazole and tetracycline (10(-5) to 10(-6)) than for C10:0 MG, C12:0 MG, and C12:0 FFA (< 10(-8)). Collectively, our data demonstrate that H. pylori is rapidly inactivated by medium-chain MGs and lauric acid and exhibits a relatively low frequency of spontaneous development of resistance to the bactericidal activity of MGs. Further studies are needed to establish whether MGs may be useful either alone or with other known therapeutic agents in the management of H. pylori infections in humans.
先前的研究表明,各种短链和中链游离脂肪酸(FFA)及其相应的单酰甘油酯(MG)在体外对主要革兰氏阳性菌具有抗菌活性。最近的研究还表明,幽门螺杆菌属的生长受到亚油酸和花生四烯酸的抑制。本研究的目的是评估幽门螺杆菌对中链MG和FFA体外杀菌特性的敏感性。将幽门螺杆菌与碳链长度从C10:0到C14:0的饱和MG在1 mM浓度下孵育1小时后,活菌数量减少了4个对数单位或更多。观察到C9:0、C15:0和C16:0 MG的杀菌活性较低。相比之下,月桂酸(C12:0)是唯一对幽门螺杆菌具有杀菌活性的中链饱和FFA。MG和FFA在中性或酸性pH下孵育仅15分钟后即具有杀菌作用。在液体饮食中蛋白质含量较高的情况下,需要更高水平的MG和FFA才能产生杀菌活性。我们还发现,幽门螺杆菌对甲硝唑和四环素的自发耐药频率(10^(-5)至10^(-6))高于对C10:0 MG、C12:0 MG和C12:0 FFA的自发耐药频率(<10^(-8))。总体而言,我们的数据表明,幽门螺杆菌可被中链MG和月桂酸迅速灭活,并且对MG杀菌活性的自发耐药频率相对较低。需要进一步研究来确定MG单独或与其他已知治疗药物联合使用是否对人类幽门螺杆菌感染的治疗有用。