Control of Bacterial Persister Cells by Trp/Arg-Containing Antimicrobial Peptides
Control of Bacterial Persister Cells by Trp/Arg-Containing Antimicrobial Peptides
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DOI：
10.1128/aem.02440-10
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发表时间：
2011-07-01
影响因子：
4.4
通讯作者：
Ren, Dacheng
中科院分区：
文献类型：
--
作者：
Chen, Xi;Zhang, Mi;Ren, Dacheng
持留细胞是细菌群体中固有的休眠表型变体。它们在慢性感染中起重要作用，并且由于与相同基因型的正常细胞相比对抗生素的耐受性极大增强而对治疗提出了巨大挑战。在这项研究中，我们报告，阳离子膜穿透肽含有不同数量的精氨酸和色氨酸重复是有效的，在杀死大肠杆菌HM 22，一个hyper-persister生产者的persister细胞。比较了三种线性肽[（RW）（n）-NH 2，其中n为2、3或4]和树枝状肽（RW）（4D）在杀死细菌持留菌中的活性。尽管树状肽（RW）（4D）需要较低的阈值来杀死强直性持留细胞，但八聚体肽（RW）（4）-NH 2在高浓度下对强直性持留细胞最有效。例如，用80 μ M（RW）（4）-NH 2处理60分钟导致活的持留细胞数量减少99.7%。（RW）（4）-NH 2和（RW）（4D）也显著降低了驻留在表面附着生物膜中的持续细胞的活力。这两种肽也被发现显着增强生物膜细胞对氧氟沙星的敏感性。（RW）（4）-NH 2的效力进一步通过其分散和杀死具有高百分比的持留细胞的预形成生物膜的能力来标记。有趣的是，发现大约70%的分散细胞已经失去了其固有的耐受性，并且如果不被该肽直接杀死，则变得对氨苄青霉素敏感。这些结果有助于更好地了解这些肽的活性，并可能有助于未来开发更有效的慢性感染治疗方法。
Persister cells are dormant phenotypic variants inherent in a bacterial population. They play important roles in chronic infections and present great challenges to therapy due to extremely enhanced tolerance to antibiotics compared to that of normal cells of the same genotype. In this study, we report that cationic membrane-penetrating peptides containing various numbers of arginine and tryptophan repeats are effective in killing persister cells of Escherichia coli HM22, a hyper-persister producer. The activities of three linear peptides [(RW)(n)-NH2, where n is 2, 3, or 4] and a dendrimeric peptide, (RW)(4D), in killing bacterial persisters were compared. Although the dendrimeric peptide (RW)(4D) requires a lower threshold to kill planktonic persisters, octameric peptide (RW)(4)-NH2 is the most effective against planktonic persister cells at high concentrations. For example, treatment with 80 mu M (RW)(4)-NH2 for 60 min led to a 99.7% reduction in the number of viable persister cells. The viability of persister cells residing in surface-attached biofilms was also significantly reduced by (RW)(4)-NH2 and (RW)(4D). These two peptides were also found to significantly enhance the susceptibility of biofilm cells to ofloxacin. The potency of (RW)(4)-NH2 was further marked by its ability to disperse and kill preformed biofilms harboring high percentages of persister cells. Interestingly, approximately 70% of the dispersed cells were found to have lost their intrinsic tolerance and become susceptible to ampicillin if not killed directly by this peptide. These results are helpful for better understanding the activities of these peptides and may aid in future development of more effective therapies of chronic infections.