Polyamines increase antibiotic susceptibility in Pseudomonas aeruginosa
Polyamines increase antibiotic susceptibility in Pseudomonas aeruginosa
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DOI：
10.1128/aac.50.5.1623-1627.2006
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发表时间：
2006-05-01
影响因子：
4.9
通讯作者：
Lu, CD
中科院分区：
文献类型：
--
作者：
Kwon, DH;Lu, CD
铜绿假单胞菌是一种机会致病菌。治疗因对抗假单胞菌治疗的频繁获得性耐药性而变得复杂。多胺（尸胺、腐胺、亚精胺和精胺）是所有生物体所必需的普遍存在的聚阳离子化合物。多胺以剂量依赖性方式增加铜绿假单胞菌对1.4 β-内酰胺类抗生素、氯霉素、萘啶酸和甲氧苄啶的敏感性，如MIC降低高达64倍所示。这种作用部分拮抗（25至50%）的存在下，10 MM的Mg 2+或Ca 2+。与此相反，外膜透化剂，多粘菌素B九肽和EDTA的效果，完全取消3 mM Mg 2+或Ca 2+。通过周质β-内酰胺酶的活性测量来评估这些化合物对外膜屏障的变化。结果表明，EDTA和多粘菌素B如预期的那样作为外膜破坏剂，外源亚精胺和精胺对外膜渗透性或破裂没有表现出任何明显的影响。总之，这些结果强烈表明，多胺增加抗生素敏感性的机制与EDTA和多粘菌素B不同。多胺可能通过增加某些β-内酰胺类抗生素的有效性而在抗假单胞菌疗法中潜在地有用。
Pseudomonas aeruginosa is an opportunistic human pathogen. Treatment is complicated by frequent acquired resistance to antipseudomonal therapies. Polyamines (cadaverine, putrescine, spermidine, and spermine) are ubiquitous polycationic compounds essential for all living organisms. In a dose-dependent manner, polyamines increased the susceptibility of P. aeruginosa to 1.4 beta-lactam antibiotics, chloramphenicol, nalidixic acid, and trimethoprim as demonstrated by a reduction in MIC of up to 64-fold. This effect was partially antagonized (25 to 50%) by the presence of 10 MM Of Mg2+ or Ca2+. In contrast, the effects of the outer membrane permeabilizers, polymyxin B nonapeptide and EDTA, were completely abolished by 3 mM Mg2+ or Ca2+. Changes on the outer membrane barrier by these compounds were assessed by activity measurements of periplasmic beta-lactamase. The results showed that while EDTA and polymyxin B serve as outer membrane disorganizing agents as expected, exogenous spermidine and spermine did not exhibit any apparent effect on outer membrane permeability or rupture. In summary, these results strongly suggest that the increased antibiotic susceptibility by polyamines is exerted by a mechanism that differs from that of EDTA and polymyxin B. Polyamines might be potentially useful in antipseudomonal therapies by increasing the effectiveness of certain beta-lactam antibiotics.