Chemical communication of antibiotic resistance by a highly resistant subpopulation of bacterial cells.
Chemical communication of antibiotic resistance by a highly resistant subpopulation of bacterial cells.
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DOI：
10.1371/journal.pone.0068874
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Valvano MA
中科院分区：
文献类型：
--
作者：
El-Halfawy OM;Valvano MA
细菌群体的整体抗生素耐药性是细菌细胞亚群所表现出的广泛敏感性的综合结果。一些机会性革兰氏阴性菌对抗生素有异耐药，但其异耐药机制尚不清楚。我们使用新绿伯克霍尔德菌作为机会性细菌的模型来研究对抗菌肽多粘菌素B （PmB）和其他杀菌抗生素反应的异质性的影响。在这里，我们报道了白葡萄球菌对PmB具有异抗性。种群分析分析还发现，从看似同质的培养中产生的新绿囊孢杆菌亚群比培养中的其他细胞对更高水平的多粘菌素B具有抗性，并且可以保护更敏感的细胞不被杀死，以及来自其他物种的敏感细菌，如铜绿假单胞菌和大肠杆菌。抗性的传递依赖于腐胺合成和YceI的上调，YceI是一种广泛保守的低分子量分泌蛋白。缺失腐胺和YceI合成基因可使其丧失保护作用，而药物抑制腐胺合成可降低对多粘菌素b的抗性。多胺和YceI也是新绿芽孢杆菌对多种抗菌药物的异源耐药所必需的。我们认为腐胺和YceI类似于“危险的”信息化学物质，其细菌亚群的产量增加，对杀菌抗生素产生更强的耐药性，从而向同一或不同物种中更敏感的群体成员传递更高水平的耐药性。
The overall antibiotic resistance of a bacterial population results from the combination of a wide range of susceptibilities displayed by subsets of bacterial cells. Bacterial heteroresistance to antibiotics has been documented for several opportunistic Gram-negative bacteria, but the mechanism of heteroresistance is unclear. We use Burkholderia cenocepacia as a model opportunistic bacterium to investigate the implications of heterogeneity in the response to the antimicrobial peptide polymyxin B (PmB) and also other bactericidal antibiotics. Here, we report that B. cenocepacia is heteroresistant to PmB. Population analysis profiling also identified B. cenocepacia subpopulations arising from a seemingly homogenous culture that are resistant to higher levels of polymyxin B than the rest of the cells in the culture, and can protect the more sensitive cells from killing, as well as sensitive bacteria from other species, such as Pseudomonas aeruginosa and Escherichia coli. Communication of resistance depended on upregulation of putrescine synthesis and YceI, a widely conserved low-molecular weight secreted protein. Deletion of genes for the synthesis of putrescine and YceI abrogate protection, while pharmacologic inhibition of putrescine synthesis reduced resistance to polymyxin B. Polyamines and YceI were also required for heteroresistance of B. cenocepacia to various bactericidal antibiotics. We propose that putrescine and YceI resemble "danger" infochemicals whose increased production by a bacterial subpopulation, becoming more resistant to bactericidal antibiotics, communicates higher level of resistance to more sensitive members of the population of the same or different species.
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