Rieger Martin, Mauch Harald, Hakenbeck Regine
Department of Microbiology, University of Kaiserslautern, Kaiserslautern, Germany.
HELIOS Klinikum Emil Von Behring, Berlin, Germany.
mSphere. 2017 Jun 7;2(3). doi: 10.1128/mSphere.00201-17. eCollection 2017 May-Jun.
isolates of serotype 23F with intermediate penicillin resistance were recovered on seven occasions over a period of 37 months from a cystic fibrosis patient in Berlin. All isolates expressed the same multilocus sequence type (ST), ST10523. The genome sequences of the first and last isolates, D122 and D141, revealed the absence of two phage-related gene clusters compared to the genome of another ST10523 strain, D219, isolated earlier at a different place in Germany. Genomes of all three strains carried the same novel mosaic penicillin-binding protein (PBP) genes, , , and ; these genes were distinct from those of other penicillin-resistant strains except for of a Romanian isolate. All PBPs contained mutations that have been associated with the penicillin resistance phenotype. Most interestingly, a mosaic block identical to an internal sequence of ST10523 was present in of strain B93-4, which was isolated from the same patient. This suggests interspecies gene transfer from to within the host. Nearly all genes expressing surface proteins, which represent major virulence factors of and are typical for this species, were present in the genome of ST10523. One exception was the hyaluronidase gene , which contained a 12-nucleotide deletion within the promoter region and an internal stop codon. The lack of a functional hyaluronidase might contribute to the ability to persist in the host for an unusually long period of time. is a common resident in the human nasopharynx. However, carriage can result in severe diseases due to a unique repertoire of pathogenicity factors that are rare in closely related commensal streptococci. We investigated a penicillin-resistant clone of serotype 23F isolated from a cystic fibrosis patient on multiple occasions over an unusually long period of over 3 years that was present without causing disease. Genome comparisons revealed an apparent nonfunctional pneumococcus-specific gene encoding a hyaluronidase, supporting the view that this enzyme adds to the virulence potential of the bacterium. The 23F clone harbored unique mosaic genes encoding penicillin resistance determinants, the product of horizontal gene transfer involving the commensal as donor species. Sequences identical to one such mosaic gene were identified in an strain from the same patient, suggesting that in this case played the role of donor.
在37个月的时间里,从柏林一名囊性纤维化患者身上7次分离出具有中度青霉素抗性的23F血清型菌株。所有分离株均表现出相同的多位点序列类型(ST),即ST10523。与另一个ST10523菌株D219(早些时候在德国不同地点分离)的基因组相比,第一个和最后一个分离株D122和D141的基因组序列显示缺少两个与噬菌体相关的基因簇。所有三个菌株的基因组都携带相同的新型嵌合青霉素结合蛋白(PBP)基因,即 、 、 和 ;除了罗马尼亚一株 分离株的 基因外,这些基因与其他耐青霉素 菌株的基因不同。所有PBP都含有与青霉素抗性表型相关的突变。最有趣的是,在从同一患者分离的 菌株B93-4的 基因中存在一个与ST10523内部序列相同的嵌合块。这表明在宿主内从 到 的种间基因转移。几乎所有表达表面蛋白的基因(这些基因代表 的主要毒力因子且是该物种所特有的)都存在于ST10523的基因组中。一个例外是透明质酸酶基因 ,其启动子区域内有一个12个核苷酸的缺失以及一个内部终止密码子。缺乏功能性透明质酸酶可能有助于 在宿主中异常长时间地持续存在。 是人类鼻咽部的常见定植菌。然而,由于其独特的致病因子组合(在密切相关的共生链球菌中很少见),定植可能导致严重疾病。我们研究了从一名囊性纤维化患者身上在超过3年的异常长时期内多次分离出的一株耐青霉素的23F血清型 克隆,该克隆在不引起疾病的情况下存在。基因组比较揭示了一个明显无功能的编码透明质酸酶的肺炎球菌特异性基因,支持了这种酶增加细菌毒力潜力的观点。23F克隆含有独特的嵌合基因,这些基因编码青霉素抗性决定簇,是涉及共生 作为供体物种的水平基因转移的产物。在来自同一患者的一株 菌株中鉴定出与一个这样的嵌合基因相同的序列,表明在这种情况下 起到了供体的作用。