Liu Michael, Lu Jing, Müller Patrick, Turnbull Lynne, Burke Catherine M, Schlothauer Ralf C, Carter Dee A, Whitchurch Cynthia B, Harry Elizabeth J
The ithree institute, University of Technology, Sydney, Sydney, NSW Australia.
Comvita New Zealand Limited, Te Puke New Zealand.
Front Microbiol. 2015 Jan 27;5:779. doi: 10.3389/fmicb.2014.00779. eCollection 2014.
Skin infections caused by antibiotic resistant Staphylococcus aureus are a significant health problem worldwide; often associated with high treatment cost and mortality rate. Complex natural products like New Zealand (NZ) manuka honey have been revisited and studied extensively as an alternative to antibiotics due to their potent broad-spectrum antimicrobial activity, and the inability to isolate honey-resistant S. aureus. Previous studies showing synergistic effects between manuka-type honeys and antibiotics have been demonstrated against the growth of one methicillin-resistant S. aureus (MRSA) strain. We have previously demonstrated strong synergistic activity between NZ manuka-type honey and rifampicin against growth and biofilm formation of multiple S. arueus strains. Here, we have expanded our investigation using multiple S. aureus strains and four different antibiotics commonly used to treat S. aureus-related skin infections: rifampicin, oxacillin, gentamicin, and clindamycin. Using checkerboard microdilution and agar diffusion assays with S. aureus strains including clinical isolates and MRSA we demonstrate that manuka-type honey combined with these four antibiotics frequently produces a synergistic effect. In some cases when synergism was not observed, there was a significant enhancement in antibiotic susceptibility. Some strains that were highly resistant to an antibiotic when present alone become sensitive to clinically achievable concentrations when combined with honey. However, not all of the S. aureus strains tested responded in the same way to these combinational treatments. Our findings support the use of NZ manuka-type honeys in clinical treatment against S. aureus-related infections and extend their potential use as an antibiotic adjuvant in combinational therapy. Our data also suggest that manuka-type honeys may not work as antibiotic adjuvants for all strains of S. aureus, and this may help determine the mechanistic processes behind honey synergy.
由耐抗生素金黄色葡萄球菌引起的皮肤感染是一个全球性的重大健康问题，通常伴随着高昂的治疗成本和死亡率。像新西兰麦卢卡蜂蜜这样的复杂天然产物，因其强大的广谱抗菌活性以及无法分离出对蜂蜜耐药的金黄色葡萄球菌，已被重新审视并广泛研究，作为抗生素的替代品。先前的研究表明，麦卢卡型蜂蜜与抗生素之间存在协同作用，已证明对一株耐甲氧西林金黄色葡萄球菌（MRSA）的生长有抑制作用。我们之前已经证明，新西兰麦卢卡型蜂蜜与利福平对多种金黄色葡萄球菌菌株的生长和生物膜形成具有强大的协同活性。在此，我们扩大了研究范围，使用多种金黄色葡萄球菌菌株以及四种常用于治疗与金黄色葡萄球菌相关皮肤感染的不同抗生素：利福平、苯唑西林、庆大霉素和克林霉素。通过对包括临床分离株和MRSA在内的金黄色葡萄球菌菌株进行棋盘微量稀释和琼脂扩散试验，我们证明麦卢卡型蜂蜜与这四种抗生素联合使用时经常会产生协同作用。在某些未观察到协同作用的情况下，抗生素敏感性有显著提高。一些单独存在时对某种抗生素高度耐药的菌株，与蜂蜜联合使用时对临床可达到的浓度变得敏感。然而，并非所有测试的金黄色葡萄球菌菌株对这些联合治疗的反应都相同。我们的研究结果支持在临床治疗中使用新西兰麦卢卡型蜂蜜来对抗与金黄色葡萄球菌相关的感染，并扩大了其作为联合治疗中抗生素佐剂的潜在用途。我们的数据还表明，麦卢卡型蜂蜜可能并非对所有金黄色葡萄球菌菌株都能作为抗生素佐剂起作用，这可能有助于确定蜂蜜协同作用背后的机制过程。
