Sivaraman Karthikeyan, Venkataraman Nitya, Tsai Jennifer, Dewell Scott, Cole Alexander M
Department of Molecular Biology & Microbiology, Biomolecular Science Center, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, USA.
BMC Genomics. 2008 Sep 22;9:433. doi: 10.1186/1471-2164-9-433.
Nasal carriage of Staphylococcus aureus is a major risk factor in clinical and community settings due to the range of etiologies caused by the organism. We have identified unique immunological and ultrastructural properties associated with nasal carriage isolates denoting a role for bacterial factors in nasal carriage. However, despite extensive molecular level characterizations by several groups suggesting factors necessary for colonization on nasal epithelium, genetic determinants of nasal carriage are unknown. Herein, we have set a genomic foundation for unraveling the bacterial determinants of nasal carriage in S. aureus.
MLST analysis revealed no lineage specific differences between carrier and non-carrier strains suggesting a role for mobile genetic elements. We completely sequenced a model carrier isolate (D30) and a model non-carrier strain (930918-3) to identify differential gene content. Comparison revealed the presence of 84 genes unique to the carrier strain and strongly suggests a role for Type VII secretion systems in nasal carriage. These genes, along with a putative pathogenicity island (SaPIBov) present uniquely in the carrier strains are likely important in affecting carriage. Further, PCR-based genotyping of other clinical isolates for a specific subset of these 84 genes raise the possibility of nasal carriage being caused by multiple gene sets.
Our data suggest that carriage is likely a heterogeneic phenotypic trait and implies a role for nucleotide level polymorphism in carriage. Complete genome level analyses of multiple carriage strains of S. aureus will be important in clarifying molecular determinants of S. aureus nasal carriage.
由于金黄色葡萄球菌可引发多种病因,其在鼻腔的定植是临床和社区环境中的主要风险因素。我们已经确定了与鼻腔定植菌株相关的独特免疫和超微结构特性,这表明细菌因素在鼻腔定植中发挥作用。然而,尽管多个研究小组在分子水平上进行了广泛的表征,提示了在鼻上皮细胞定植所需的因素,但鼻腔定植的遗传决定因素仍然未知。在此,我们为揭示金黄色葡萄球菌鼻腔定植的细菌决定因素奠定了基因组基础。
多位点序列分型(MLST)分析显示,定植菌株和非定植菌株之间没有谱系特异性差异,这表明移动遗传元件发挥了作用。我们对一株典型的定植菌株(D30)和一株典型的非定植菌株(930918-3)进行了全基因组测序,以确定基因含量的差异。比较结果显示,定植菌株有84个独特基因,强烈提示VII型分泌系统在鼻腔定植中发挥作用。这些基因,连同仅在定植菌株中存在的一个假定的致病岛(SaPIBov),可能对影响定植很重要。此外,对其他临床分离株针对这84个基因的一个特定子集进行基于PCR的基因分型,增加了鼻腔定植可能由多个基因集引起的可能性。
我们的数据表明,定植可能是一种异质性表型特征,并暗示核苷酸水平多态性在定植中发挥作用。对多个金黄色葡萄球菌定植菌株进行全基因组水平分析,对于阐明金黄色葡萄球菌鼻腔定植的分子决定因素至关重要。