Brown Jeremy S, Gilliland Sarah M, Spratt Brian G, Holden David W
Centre for Respiratory Research, Department of Medicine, Rayne Institute, Royal Free and University College Medical School, London WC1E 6JJ, United Kingdom.
Infect Immun. 2004 Mar;72(3):1587-93. doi: 10.1128/IAI.72.3.1587-1593.2004.
We have previously described a 27-kb pathogenicity island of Streptococcus pneumoniae, termed pneumococcal pathogenicity island 1 (PPI1), which contains iron uptake locus piaABCD, required for full virulence in mice, and a further 28 previously uncharacterized genes. We have investigated one of these, Sp1051, which encodes a protein of unknown function. Disruption of Sp1051 does not affect growth in laboratory broth, serum, or blood but impairs virulence in mouse models of infection. When S. pneumoniae capsular serotypes were analyzed by PCR and Southern hybridization, it was found that 33% did not contain Sp1051. Analysis of other genes within PPI1 demonstrated that, compared to the serotype 4 genome published by The Institute for Genome Research (TIGR), the genomes of many strains contain deletions of a variable number of genes between Sp1046 and Sp1064, conforming to one of six different patterns. Amplification by PCR of this PPI1 variable region from a capsular serotype 17 strain and comparison of the sequence to TIGR serotype 4 strain sequence showed that Sp1051 is contained within an 11.3-kb segment of DNA flanked by 7-bp direct repeats within the serotype 4 strain which is not present in the serotype 17 strain. Further comparison of the sequences of this region between the three published S. pneumoniae genomes demonstrated that serotype 19F and strain R6 contain novel complements of genes not present in the serotype 4 strain. These data indicate that there is striking variation in gene content and structure of the 3' region of PPI1 among strains and that this region includes at least one virulence determinant. Gene variation within horizontally acquired DNA such as that of PPI1 may be one factor modulating differences in virulence among strains.
我们之前曾描述过肺炎链球菌的一个27 kb的致病岛，称为肺炎球菌致病岛1（PPI1），它包含铁摄取位点piaABCD（小鼠完全致病所需）以及另外28个以前未鉴定的基因。我们研究了其中一个基因Sp1051，它编码一种功能未知的蛋白质。破坏Sp1051不影响在实验室肉汤、血清或血液中的生长，但会损害感染小鼠模型中的毒力。通过PCR和Southern杂交分析肺炎链球菌荚膜血清型时，发现33%不含有Sp1051。对PPI1内的其他基因进行分析表明，与基因组研究所（TIGR）公布的4型血清型基因组相比，许多菌株的基因组在Sp1046和Sp1064之间含有数量可变的基因缺失，符合六种不同模式之一。从17型荚膜血清型菌株中通过PCR扩增该PPI1可变区，并将序列与TIGR 4型血清型菌株序列进行比较，结果显示Sp1051包含在4型血清型菌株中一个11.3 kb的DNA片段内，该片段两侧为7 bp的直接重复序列，而17型血清型菌株中不存在。对已公布的三个肺炎链球菌基因组之间该区域的序列进行进一步比较表明，19F血清型和R6菌株含有4型血清型菌株中不存在的新基因组合。这些数据表明，菌株间PPI1 3'区域的基因含量和结构存在显著差异，且该区域至少包含一个毒力决定因素。水平获得的DNA（如PPI1）内的基因变异可能是调节菌株间毒力差异的一个因素。
