Turkington Christopher J R, Morozov Andrew, Clokie Martha R J, Bayliss Christopher D
Department of Genetics and Genome Biology, University of Leicester, Leicester, United Kingdom.
Department of Mathematics, University of Leicester, Leicester, United Kingdom.
Front Microbiol. 2019 Jul 5;10:1473. doi: 10.3389/fmicb.2019.01473. eCollection 2019.
Hypermutable loci are widespread in bacteria as mechanisms for rapid generation of phenotypic diversity within a population that enables survival of fluctuating, often antagonistic, selection pressures. Localized hypermutation can mediate phase variation and enable survival of bacteriophage predation due to high frequency, reversible alterations in the expression of phage receptors. As phase variation can also generate population-to-population heterogeneity, we hypothesized that this phenomenon may facilitate survival of spatially-separated bacterial populations from phage invasion in a manner analogous to herd immunity to infectious diseases in human populations. The gene of is subject to "ON" and "OFF" switches in expression mediated by mutations in a 5'CAAT repeat tract present within the reading frame. The enzyme encoded by mediates addition of a galactose moiety of the lipopolysaccharide. This moiety is required for attachment of the HP1C1 phage such that the ON state of the gene is associated with HP1c1 susceptibility while the OFF state is resistant to infection. We developed an "oscillating prey assay" to examine phage spread through a series of sub-populations of whose phage receptor is in an ON or OFF state. Phage extinction was frequently observed when the proportion of phage-resistant sub-populations exceeded 34%. modeling indicated that phage extinction was interdependent on phage loss during transfer between sub-populations and the frequency of resistant sub-populations. In a fixed-area oscillating prey assay, heterogeneity in phage resistance was observed to generate vast differences in phage densities across a meta-population of multiple bacterial sub-populations resulting in protective quarantining of some sub-populations from phage attack. We conclude that phase-variable hypermutable loci produce bacterial "herd immunity" with resistant intermediary-populations acting as a barricade to reduce the viral load faced by phage-susceptible sub-populations. This paradigm of meta-population protection is applicable to evolution of hypermutable loci in multiple bacteria-phage and host-pathogen interactions.
高变位点在细菌中广泛存在，作为一种机制，可在种群内快速产生表型多样性，从而使细菌能够在波动的、通常具有对抗性的选择压力下生存。局部高突变可介导相变，并由于噬菌体受体表达的高频、可逆变化而使细菌能够在噬菌体捕食中存活。由于相变也可产生种群间的异质性，我们推测这种现象可能以类似于人类群体中传染病群体免疫的方式，促进空间分离的细菌种群免受噬菌体入侵。 的基因在阅读框内存在的5'CAAT重复序列中的突变介导的表达中经历“开”和“关”切换。 编码的酶介导脂多糖半乳糖部分的添加。该部分是HP1C1噬菌体附着所必需的，因此 基因的“开”状态与对HP1c1的易感性相关，而“关”状态则对感染具有抗性。我们开发了一种“振荡猎物试验”，以检查噬菌体通过其噬菌体受体处于“开”或“关”状态的一系列 亚群的传播情况。当抗噬菌体亚群的比例超过34%时，经常观察到噬菌体灭绝。建模表明，噬菌体灭绝与亚群间转移过程中的噬菌体损失以及抗性亚群的频率相互依赖。在固定面积的振荡猎物试验中，观察到噬菌体抗性的异质性在多个细菌亚群的集合种群中产生了噬菌体密度的巨大差异，从而导致一些亚群受到保护而免受噬菌体攻击。我们得出结论，相变可变的高变位点产生细菌“群体免疫”，抗性中间种群起到屏障作用，以减少噬菌体易感亚群面临的病毒载量。这种集合种群保护模式适用于多种细菌-噬菌体和宿主-病原体相互作用中高变位点的进化。
