Epigenetic Control of Salmonella enterica O-Antigen Chain Length: A Tradeoff between Virulence and Bacteriophage Resistance.
Epigenetic Control of Salmonella enterica O-Antigen Chain Length: A Tradeoff between Virulence and Bacteriophage Resistance.
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DOI：
10.1371/journal.pgen.1005667
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发表时间：
2015-11
期刊：
影响因子：
4.5
通讯作者：
Casadesús J
中科院分区：
文献类型：
--
作者：
Cota I;Sánchez-Romero MA;Hernández SB;Pucciarelli MG;García-Del Portillo F;Casadesús J
肠道沙门氏菌opvAB操纵子是一个水平获得的基因座，在Dam甲基化控制下经历相位变化。OpvA和OpvB蛋白在内膜中形成缠绕的条带。OpvA和OpvB的合成改变了脂多糖O-抗原链的长度，并赋予对噬菌体9 NA（Siphoviridae）、Det 7（Myoviridae）和P22（Podoviridae）的抗性。它们以O抗原为受体。由于opvAB经历了相变，S.肠道培养物含有opvAB OFF和opvAB ON细胞的亚群。在使用0-抗原作为受体的噬菌体存在下，杀死opvAB OFF亚群并选择opvAB ON亚群。通过O-抗原链长度的相位变化获得噬菌体抗性需要回报：opvAB表达降低沙门氏菌的毒力。然而，一旦噬菌体攻击停止，相变化允许opvAB OFF亚群的复苏。因此，由opvAB相变异产生的表型异质性使沙门氏菌预先适应噬菌体挑战而存活，适应性成本仅是短暂的。权衡可以增加生物体的适应能力，但代价是降低特定性状赋予的适应性。这项研究描述了一个权衡，赋予噬菌体抗性肠道沙门氏菌的代价是降低其致病能力。opvAB操纵子的相位变化产生两个细菌细胞亚群，每个亚群具有不同的脂多糖结构。一个亚群是大的和有毒的，但对使用脂多糖O-抗原作为受体的噬菌体敏感，而另一个是小的和无毒的，但噬菌体抗性。在靶向O抗原的噬菌体存在下，只有无毒力亚群存活。然而，一旦噬菌体攻击停止，相变化允许毒性opvAB OFF亚群的复苏。这种短暂的权衡可能说明了以可逆方式产生细菌亚群的表观遗传机制的适应价值。
The Salmonella enterica opvAB operon is a horizontally-acquired locus that undergoes phase variation under Dam methylation control. The OpvA and OpvB proteins form intertwining ribbons in the inner membrane. Synthesis of OpvA and OpvB alters lipopolysaccharide O-antigen chain length and confers resistance to bacteriophages 9NA (Siphoviridae), Det7 (Myoviridae), and P22 (Podoviridae). These phages use the O-antigen as receptor. Because opvAB undergoes phase variation, S. enterica cultures contain subpopulations of opvAB OFF and opvAB ON cells. In the presence of a bacteriophage that uses the O-antigen as receptor, the opvAB OFF subpopulation is killed and the opvAB ON subpopulation is selected. Acquisition of phage resistance by phase variation of O-antigen chain length requires a payoff: opvAB expression reduces Salmonella virulence. However, phase variation permits resuscitation of the opvAB OFF subpopulation as soon as phage challenge ceases. Phenotypic heterogeneity generated by opvAB phase variation thus preadapts Salmonella to survive phage challenge with a fitness cost that is transient only. A tradeoff can increase the adaptive capacity of an organism at the expense of lowering the fitness conferred by specific traits. This study describes a tradeoff that confers bacteriophage resistance in Salmonella enterica at the expense of reducing its pathogenic capacity. Phase variation of the opvAB operon creates two subpopulations of bacterial cells, each with a distinct lipopolysaccharide structure. One subpopulation is large and virulent but sensitive to phages that use the lipopolysaccharide O-antigen as receptor, while the other is small and avirulent but phage resistant. In the presence of a phage that targets the O-antigen, only the avirulent subpopulation survives. However, phase variation permits resuscitation of the virulent opvAB OFF subpopulation as soon as phage challenge ceases. This transient tradeoff may illustrate the adaptive value of epigenetic mechanisms that generate bacterial subpopulations in a reversible manner.