Nontypeable pneumococci can be divided into multiple cps types, including one type expressing the novel gene pspK.
Nontypeable pneumococci can be divided into multiple cps types, including one type expressing the novel gene pspK.
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作者：
Park IH;Kim KH;Andrade AL;Briles DE;McDaniel LS;Nahm MH
虽然肺炎链球菌的毒力与其被膜有关，但一些致病性肺炎链球菌没有被膜，并且在血清学上是不可分型的(NT)。我们获得了按传统标准鉴定为NT“肺炎球菌”的分离株(即符合肺炎链球菌传统定义但没有基于多位点序列分型的定义的细菌)。均为视神经敏感型，有lytA，63例有PLY。12个分离物具有CPSA，这表明存在一个常规的但有缺陷的荚膜多糖合成(Cps)基因。52株CpSA阴性菌株可根据其cps基因座上的Alic(Alib-like ORF1)、Alid(Alib-like ORF2)和我们新发现的基因pspK分为三个零胶囊分支(NCC)。PspK编码一种含有LPxTG基序和YPT基序的长α螺旋区的蛋白质，已知与人的pIgR结合。NCC1有9株(pspK+，Alic和Alid阴性)，NCC2有32株(Alic+Alid+，pspK阴性)，NCC3有11株(Alid+，Alic和pspK阴性)。在52株CPSA阴性菌株中，经MLST分析鉴定为肺炎链球菌41株。所有NCC1和大多数NCC2分离株都是肺炎链球菌，而所有9株NCC3和2株NCC2都不是肺炎链球菌。来自多个个人的几个NCC1和NCC2分离株具有相同的MLST和cps区域，表明未被包膜的肺炎链球菌可以在人类之间传播。此外，NCC1和NCC2肺炎链球菌分离株可以定植小鼠和包裹肺炎链球菌，尽管带有人为破坏cps基因座的肺炎链球菌不能。此外，pspK缺失的NCC1分离株没有在小鼠身上定植，这表明pspK对定植至关重要。因此，PspK可能为肺炎球菌提供了一种在鼻咽内无包膜的生存方式。胶囊的存在对包括肺炎球菌在内的许多致病菌来说是至关重要的。肺炎球菌疫苗的设计目的是激发抗囊抗体，以反映肺炎球菌胶囊的致病重要性。肺炎球菌被膜致病重要性的另一个证据是，在肺炎球菌中，产生被膜所必需的所有基因都在一个遗传位点上，该基因被称为cps基因座。然而，偶尔也会有致病性肺炎球菌没有包膜，它们如何在没有包膜的宿主中生存尚不清楚。在这里，我们发现在这些无囊型肺炎球菌中，cps基因已经被各种新的基因取代，它们可以在小鼠鼻咽和被囊化的肺炎球菌中定植。由于取代cps基因座的基因在宿主生存中可能很重要，它们可能显示出肺炎球菌使用的新的和/或替代的包膜非依赖性生存机制。
Although virulence of Streptococcus pneumoniae is associated with its capsule, some pathogenic S. pneumoniae isolates lack capsules and are serologically nontypeable (NT). We obtained 64 isolates that were identified as NT “pneumococci” (i.e., bacteria satisfying the conventional definition but without the multilocus sequence typing [MLST]-based definition of S. pneumoniae) by the traditional criteria. All 64 were optochin sensitive and had lytA, and 63 had ply. Twelve isolates had cpsA, suggesting the presence of a conventional but defective capsular polysaccharide synthesis (cps) locus. The 52 cpsA-negative isolates could be divided into three null capsule clades (NCC) based on aliC (aliB-like ORF1), aliD (aliB-like ORF2), and our newly discovered gene, pspK, in their cps loci. pspK encodes a protein with a long alpha-helical region containing an LPxTG motif and a YPT motif known to bind human pIgR. There were nine isolates in NCC1 (pspK+ but negative for aliC and aliD), 32 isolates in NCC2 (aliC+ aliD+ but negative for pspK), and 11 in NCC3 (aliD+ but negative for aliC and pspK). Among 52 cpsA-negative isolates, 41 were identified as S. pneumoniae by MLST analysis. All NCC1 and most NCC2 isolates were S. pneumoniae, whereas all nine NCC3 and two NCC2 isolates were not S. pneumoniae. Several NCC1 and NCC2 isolates from multiple individuals had identical MLST and cps regions, showing that unencapsulated S. pneumoniae can be infectious among humans. Furthermore, NCC1 and NCC2 S. pneumoniae isolates could colonize mice as well as encapsulated S. pneumoniae, although S. pneumoniae with an artificially disrupted cps locus did not. Moreover, an NCC1 isolate with pspK deletion did not colonize mice, suggesting that pspK is critical for colonization. Thus, PspK may provide pneumococci a means of surviving in the nasopharynx without capsule. The presence of a capsule is critical for many pathogenic bacteria, including pneumococci. Reflecting the pathogenic importance of the pneumococcal capsule, pneumococcal vaccines are designed to elicit anticapsule antibodies. Additional evidence for the pathogenic importance of the pneumococcal capsule is the fact that in pneumococci all the genes necessary for capsule production are together in one genetic locus, which is called the cps locus. However, there are occasional pathogenic pneumococci without capsules, and how they survive in the host without the capsule is unknown. Here, we show that in these acapsular pneumococci, the cps loci have been replaced with various novel genes and they can colonize mouse nasopharynges as well as capsulated pneumococci. Since the genes that replace the cps loci are likely to be important in host survival, they may show new and/or alternative capsule-independent survival mechanisms used by pneumococci.