Genomic and transcriptomic differences in community acquired methicillin resistant Staphylococcus aureus USA300 and USA400 strains
Genomic and transcriptomic differences in community acquired methicillin resistant Staphylococcus aureus USA300 and USA400 strains
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DOI：
10.1186/1471-2164-15-1145
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发表时间：
2014-12-19
期刊：
影响因子：
4.4
通讯作者：
Daum, Robert S.
中科院分区：
文献类型：
--
作者：
Jones, Marcus B.;Montgomery, Christopher P.;Daum, Robert S.
背景资料：金黄色葡萄球菌（Staphylococcus aureus）是一种人类病原体，通过其引起包括菌血症、肺炎和软组织感染在内的多种人类感染的能力而导致大量发病率和死亡率。最令人担忧的是耐甲氧西林金黄色葡萄球菌菌株（MRSA）的出现和传播，这些菌株对几乎所有β-内酰胺类抗生素都有耐药性。USA 300 MRSA基因背景在社区相关的S.结果：为了更好地了解金黄色葡萄球菌（S. aureus infections，CA-MRSA）的潜在适应性优势和毒力能力，我们对美国400株CA-MRSA菌株进行了研究。为了获得金黄色葡萄球菌USA 300克隆，我们对15株USA 300和4株USA 400临床分离株进行了全基因组测序。USA 300和USA 400脉型的代表性基因组的比较表明了移动的基因组元件的许多差异。我们通过微阵列杂交检查了体外基因表达谱，并通过进行全基因组qRT-PCR分析检查了USA 300和USA 400 MRSA菌株在小鼠肺部感染期间的体内转录组。与USA 400相比，USA 300中6种外毒素的独特存在和表达增加（12至600倍）可能有助于USA 300克隆的毒力增加。重要的是，我们还观察到USA 300中前噬菌体基因的上调，（与USA 400相比）（包括由前噬菌体Phi Sa 2usa和Phi Sa 3usa编码的基因），表明这些前噬菌体可能通过促进USA 300克隆的毒力特性的提高而在体内发挥重要作用。我们观察到USA 300和USA 400菌株的遗传内容的差异，以及肺肺炎模型中移动的元件的体外和体内基因表达的显著差异。这是第一个研究记录USA 300和USA 400菌株在体外和体内生长过程中的整体转录差异。
Background: Staphylococcus aureus is a human pathogen responsible for substantial morbidity and mortality through its ability to cause a number of human infections including bacteremia, pneumonia and soft tissue infections. Of great concern is the emergence and dissemination of methicillin-resistant Staphylococcus aureus strains (MRSA) that are resistant to nearly all beta-lactams. The emergence of the USA300 MRSA genetic background among community associated S. aureus infections (CA-MRSA) in the USA was followed by the disappearance of USA400 CA-MRSA isolates.Results: To gain a greater understanding of the potential fitness advantages and virulence capacity of S. aureus USA300 clones, we performed whole genome sequencing of 15 USA300 and 4 USA400 clinical isolates. A comparison of representative genomes of the USA300 and USA400 pulsotypes indicates a number of differences in mobile genome elements. We examined the in vitro gene expression profiles by microarray hybridization and the in vivo transcriptomes during lung infection in mice of a USA300 and a USA400 MRSA strain by performing complete genome qRT-PCR analysis. The unique presence and increased expression of 6 exotoxins in USA300 (12- to 600-fold) compared to USA400 may contribute to the increased virulence of USA300 clones. Importantly, we also observed the up-regulation of prophage genes in USA300 (compared with USA400) during mouse lung infection (including genes encoded by both prophages Phi Sa2usa and Phi Sa3usa), suggesting that these prophages may play an important role in vivo by contributing to the elevated virulence characteristic of the USA300 clone.Conclusions: We observed differences in the genetic content of USA300 and USA400 strains, as well as significant differences of in vitro and in vivo gene expression of mobile elements in a lung pneumonia model. This is the first study to document the global transcription differences between USA300 and USA400 strains during both in vitro and in vivo growth.