Leaky resistance and the conditions for the existence of lytic bacteriophage
Leaky resistance and the conditions for the existence of lytic bacteriophage
复制标题
DOI：
10.1371/journal.pbio.2005971
复制
发表时间：
2018-08-01
期刊：
影响因子：
9.8
通讯作者：
Levin, Bruce R.
中科院分区：
文献类型：
--
作者：
Chaudhry, Waqas N.;Pleska, Maros;Levin, Bruce R.
在实验培养物中，当细菌与裂解性（毒性）噬菌体混合时，对噬菌体具有抗性的细菌细胞通常会出现并成为细菌的优势种群。随着抗性突变体的增加，这些简单群落中的细菌密度受到资源而不是噬菌体的限制。尽管噬菌体不能在其上复制的抗性宿主进化，但裂解性噬菌体群体最常见地与抗性细菌维持在明显稳定的状态。已经提出了几种机制来解释这一结果。在这里，我们报告的结果与噬菌体λ，λ（VIR），和大肠杆菌在连续转移培养物的毒性突变体的人口动态/进化实验。我们发现，在上升的lambda（VIR）耐药细菌，lambda（VIR）是维持在大多数情况下，在麦芽糖限制的基本培养基，并在所有情况下，在营养丰富的肉汤。利用数学模型和实验，我们表明，在这些资源有限的群体中，负责维持λ（VIR）的主要机制是由抗性E。大肠杆菌是从抗性到易感性的表型或遗传转变的高速率，这是一种迄今为止尚未证实的机制，我们称之为“漏抗性”。我们讨论了渗漏抗性对我们理解噬菌体在细菌种群中维持的条件--它们的“存在条件”的影响。"
In experimental cultures, when bacteria are mixed with lytic ( virulent) bacteriophage, bacterial cells resistant to the phage commonly emerge and become the dominant population of bacteria. Following the ascent of resistant mutants, the densities of bacteria in these simple communities become limited by resources rather than the phage. Despite the evolution of resistant hosts, upon which the phage cannot replicate, the lytic phage population is most commonly maintained in an apparently stable state with the resistant bacteria. Several mechanisms have been put forward to account for this result. Here we report the results of population dynamic/evolution experiments with a virulent mutant of phage Lambda, lambda(VIR), and Escherichia coli in serial transfer cultures. We show that, following the ascent of lambda(VIR) resistant bacteria, lambda(VIR) is maintained in the majority of cases in maltose-limited minimal media and in all cases in nutrient-rich broth. Using mathematical models and experiments, we show that the dominant mechanism responsible for maintenance of lambda(VIR) in these resource-limited populations dominated by resistant E. coli is a high rate of either phenotypic or genetic transition from resistance to susceptibility-a hitherto undemonstrated mechanism we term "leaky resistance." We discuss the implications of leaky resistance to our understanding of the conditions for the maintenance of phage in populations of bacteria-their "existence conditions."