Blomberg C, Dagerhamn J, Dahlberg S, Browall S, Fernebro J, Albiger B, Morfeldt E, Normark S, Henriques-Normark B
Swedish Institute for Infectious Disease Control, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solna, Sweden.
J Infect Dis. 2009 Apr 1;199(7):1032-42. doi: 10.1086/597205.
The invasive disease potential (IDP) of Streptococcus pneumoniae differs between serotypes, but the reason for this is unknown.
A total of 47 pneumococcal isolates from 13 serotypes with different IDPs in humans that belonged to 37 multilocus sequence types were compared by whole genome microarrays and mutant analyses.
Approximately 34% of the genes were variable, including 95 genes previously shown by signature-tagged mutagenesis (STM) to be required for invasive disease in mice. Many variable genes were localized to 41 accessory regions (ARs), of which 24 contained genes previously identified by STM as required for invasive disease. Only AR6 and AR34 were preferentially found in isolates of serotypes with high IDPs. Neither AR6, which carries a gene previously identified bySTMas required for invasive disease and encodes a 6-phospho-betaglucosidase, nor the putative adhesin expressed by AR34 was required for mouse virulence in TIGR4.
Pneumococci possess a repertoire of ARs that differ between clones and even between isolates of the same clone. The ARs required for invasive disease in humans may be redundant, as no unique pattern distinguished the most invasive clones from others. The ARs that contained genes previously identified by STM as required for virulence in mice were frequently absent from invasive human isolates. Only 1 AR (AR6) was present in almost all isolates from the serotypes with the highest IDP (1, 4, and 7F), whereas it was missing from many others.
肺炎链球菌的侵袭性疾病潜力(IDP)在不同血清型之间存在差异,但其原因尚不清楚。
通过全基因组微阵列和突变分析,比较了来自13种血清型、具有不同人类IDP、属于37种多位点序列类型的47株肺炎球菌分离株。
约34%的基因存在变异,其中包括95个先前通过签名标签诱变(STM)显示在小鼠侵袭性疾病中必需的基因。许多可变基因定位于41个辅助区域(ARs),其中24个包含先前通过STM鉴定为侵袭性疾病所需的基因。仅在具有高IDP的血清型分离株中优先发现AR6和AR34。携带先前通过STM鉴定为侵袭性疾病所需基因并编码6-磷酸-β-葡萄糖苷酶的AR6,以及AR34表达的假定黏附素,在TIGR4小鼠毒力中均非必需。
肺炎球菌拥有一系列辅助区域,这些区域在克隆之间甚至同一克隆的分离株之间都有所不同。人类侵袭性疾病所需的辅助区域可能是冗余的,因为没有独特模式能将侵袭性最强的克隆与其他克隆区分开来。先前通过STM鉴定为小鼠毒力所需基因的辅助区域在侵袭性人类分离株中常常缺失。几乎所有IDP最高的血清型(1、4和7F)的分离株中仅存在1个辅助区域(AR6),而许多其他分离株中则没有。