Phase variation in pneumococcal populations during carriage in the human nasopharynx
Phase variation in pneumococcal populations during carriage in the human nasopharynx
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DOI：
10.1038/s41598-020-58684-2
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发表时间：
2020-02-04
影响因子：
4.6
通讯作者：
Oggioni, M. R.
中科院分区：
文献类型：
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作者：
De Ste Croix, M.;Mitsi, E.;Oggioni, M. R.
肺炎链球菌是世界上主要的细菌病原体之一，导致肺炎、败血症和脑膜炎。鼻咽部的无症状定殖被认为是这些严重感染的先决条件，然而对于允许肺炎球菌从无症状定殖者转变为侵入性病原体的生物学变化知之甚少。相变量I型限制-修饰（R-M）系统（SpnIII）已与胶囊表达的变化和成功定植于小鼠鼻咽的能力相关。使用我们的实验室数据，我们已经开发了一个马尔可夫变化模型，允许预测人口内的相位变化的预期水平，并作为结果的措施时，人口偏离那些预期的随机。使用该模型，我们分析了来自实验性人类肺炎球菌携带（EHPC）项目的样本。在这里，我们表明，通过数学建模，占主导地位的SpnIII等位基因在人类鼻咽部表达的模式是显着不同的随机开关单独预测。我们的跨学科工作表明，替代甲基化模式的表达应该是肺炎球菌定植研究中的一个重要考虑因素。
Streptococcus pneumoniae is one of the world's leading bacterial pathogens, responsible for pneumonia, septicaemia and meningitis. Asymptomatic colonisation of the nasopharynx is considered to be a prerequisite for these severe infections, however little is understood about the biological changes that permit the pneumococcus to switch from asymptomatic coloniser to invasive pathogen. A phase variable type I restriction-modification (R-M) system (SpnIII) has been linked to a change in capsule expression and to the ability to successfully colonise the murine nasopharynx. Using our laboratory data, we have developed a Markov change model that allows prediction of the expected level of phase variation within a population, and as a result measures when populations deviate from those expected at random. Using this model, we have analysed samples from the Experimental Human Pneumococcal Carriage (EHPC) project. Here we show, through mathematical modelling, that the patterns of dominant SpnIII alleles expressed in the human nasopharynx are significantly different than those predicted by stochastic switching alone. Our inter-disciplinary work demonstrates that the expression of alternative methylation patterns should be an important consideration in studies of pneumococcal colonisation.