摘要

机会性病原体肺炎链球菌通常在人类鼻咽中无症状携带。由于与其他肺炎球菌菌株的高共克隆率，种内竞争相互作用部分决定了菌株的运输时间，从而决定了它们致病的可能性。这些相互作用可以由细菌素介导，例如由BLP (杆菌素- l - ike p肽)基因座编码的IIb型细菌素。为了了解BLP的多样性和进化，我们对4，418个肺炎球菌基因组进行了生物信息学分析，包括168个新测序的基因组。我们描述了基因组组织各个层次的巨大差异:基因存在/缺失、基因顺序和等位基因多样性。如果我们做出极端单纯的假设，假设这个操纵子中的所有基因可以随机分类，这种变异可能导致105种不同的细菌素相关表型，每种表型都可能代表一种独特的生态策略；然而，我们对这一极端没有实现的原因提供了几种解释。虽然稀疏分析表明，独特策略的数量并不饱和，但即使在对数千个基因组进行抽样后，我们也发现变异既不是无限的，也不是随机的。我们划分了三个细菌素组，包括组特异性细菌素、免疫基因和BLP操纵子基因序列，并认为这一组织限制了已实现的生态策略。我们还表明，肺炎球菌系统发育和克隆结构显著限制了生态策略多样性。通过检测BLP操纵子内等位基因之间的关联模式，我们发现，被认为是成对作用的细菌素基因可以发现具有广泛多样性的伴侣等位基因和免疫基因；这种等位基因保真度的总体缺乏可能是这种操纵子的流体结构的原因。我们的结果阐明了全球肺炎球菌种群中拮抗生态策略的多样性，并强调了BLP细菌素在鼻咽内竞争中的潜在作用。

The opportunistic pathogen Streptococcus pneumoniae is commonly carried asymptomatically in the human nasopharynx. Due to high rates of cocolonization with other pneumococcus strains, intraspecific competitive interactions partly determine the carriage duration of strains and thereby their potential to cause disease. These interactions may be mediated by bacteriocins, such as the type IIb bacteriocins encoded by the blp ( b acteriocin- l ike p eptide) locus. To understand blp diversity and evolution, we undertook a bioinformatic analysis of 4,418 pneumococcal genomes, including 168 newly sequenced genomes. We describe immense variation at all levels of genomic organization: Gene presence/absence, gene order, and allelic diversity. If we make the extreme and naive hypothesis that assumes all genes in this operon can assort randomly, this variation could lead to 10 15 distinct bacteriocin-related phenotypes, each potentially representing a unique ecological strategy; however, we provide several explanations for why this extreme is not realized. Although rarefaction analysis indicates that the number of unique strategies is not saturated, even after sampling thousands of genomes, we show that the variation is neither unbounded nor random. We delimit three bacteriocin groups, which contain group-specific bacteriocins, immunity genes, and blpoperon gene order, and argue that this organization places a constraint on realized ecological strategies. We additionally show that ecological strategy diversity is significantly constrained by pneumococcal phylogeny and clonal structure. By examining patterns of association between alleles within the blpoperon, we show that bacteriocin genes, which were believed to function in pairs, can be found with a broad diversity of partner alleles and immunity genes; this overall lack of allelic fidelity likely contributes to the fluid structure of this operon. Our results clarify the diversity of antagonistic ecological strategies in the global pneumococcal population and highlight the potential role of blp bacteriocins in competition within the nasopharynx.

https://academic.oup.com/gbe/article/8/4/1072/2574031