Global changes in Staphylococcus aureus gene expression in human blood.
Global changes in Staphylococcus aureus gene expression in human blood.
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DOI：
10.1371/journal.pone.0018617
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发表时间：
2011-04-15
期刊：
影响因子：
3.7
通讯作者：
DeLeo FR
中科院分区：
文献类型：
--
作者：
Malachowa N;Whitney AR;Kobayashi SD;Sturdevant DE;Kennedy AD;Braughton KR;Shabb DW;Diep BA;Chambers HF;Otto M;DeLeo FR
金黄色葡萄球菌是全球血液感染的主要原因。在美国，许多感染是由一种称为USA 300的菌株引起的。虽然取得了进展，但我们对S。促进人血液中存活并最终促进转移的金黄色葡萄球菌分子是不完整的。为此，我们分析了在人血液、人血清和胰蛋白酶大豆肉汤（TSB）（一种标准实验室培养基）中培养期间的USA 300转录组。值得注意的是，编码几种溶细胞毒素的基因在人血液中随时间上调，并且hlgA、hlgB和hlgC（编码γ-溶血素亚基HlgA、HlgB和HlgC）在所有时间点都是最高度上调的基因。与来自野生型USA 300菌株（LAC）的培养物上清液相比，来自等基因hlgABC缺失菌株（LACΔhlgABC）的培养物上清液在人中性粒细胞中形成孔并最终引起中性粒细胞溶解的能力显著降低。此外，LACΔhlgABC在小鼠菌血症模型中引起死亡的能力适度降低。另一方面，野生型和LACΔhlgABC菌株在小鼠皮肤感染模型中引起几乎相同的感染，并且这些菌株之间在体外吞噬后的细菌存活和中性粒细胞溶解相似。比较缺乏hlgABC、lukS/F-PV（编码PVL）和/或lukDE的野生型和等基因缺失菌株的培养上清液的细胞溶解能力，揭示了体外双组分白细胞毒素之间的功能冗余。这些发现，沿着白细胞毒素表达的特定生长条件的要求，可以解释任何单一的双组分白细胞毒素对USA 300免疫逃避和毒力的明显有限的贡献。
Staphylococcus aureus is a leading cause of bloodstream infections worldwide. In the United States, many of these infections are caused by a strain known as USA300. Although progress has been made, our understanding of the S. aureus molecules that promote survival in human blood and ultimately facilitate metastases is incomplete. To that end, we analyzed the USA300 transcriptome during culture in human blood, human serum, and trypticase soy broth (TSB), a standard laboratory culture media. Notably, genes encoding several cytolytic toxins were up-regulated in human blood over time, and hlgA, hlgB, and hlgC (encoding gamma-hemolysin subunits HlgA, HlgB, and HlgC) were among the most highly up-regulated genes at all time points. Compared to culture supernatants from a wild-type USA300 strain (LAC), those derived from an isogenic hlgABC-deletion strain (LACΔhlgABC) had significantly reduced capacity to form pores in human neutrophils and ultimately cause neutrophil lysis. Moreover, LACΔhlgABC had modestly reduced ability to cause mortality in a mouse bacteremia model. On the other hand, wild-type and LACΔhlgABC strains caused virtually identical abscesses in a mouse skin infection model, and bacterial survival and neutrophil lysis after phagocytosis in vitro was similar between these strains. Comparison of the cytolytic capacity of culture supernatants from wild-type and isogenic deletion strains lacking hlgABC, lukS/F-PV (encoding PVL), and/or lukDE revealed functional redundancy among two-component leukotoxins in vitro. These findings, along with a requirement of specific growth conditions for leukotoxin expression, may explain the apparent limited contribution of any single two-component leukotoxin to USA300 immune evasion and virulence.
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影响因子：
3.1
作者：
Dale, SE;Doherty-Kirby, A;Heinrichs, DE
通讯作者：
Heinrichs, DE
影响因子：
168.9
作者：
DeLeo, Frank R.;Otto, Michael;Kreiswirth, Barry N.;Chambers, Henry F.
通讯作者：
Chambers, Henry F.
影响因子：
4.5
作者：
Jenkins, Timothy C.;McCollister, Bruce D.;Burman, William J.
通讯作者：
Burman, William J.
影响因子：
6
作者：
Graham, MR;Virtaneva, K;Musser, JM
通讯作者：
Musser, JM
影响因子：
6.4
作者：
Diep, Binh An;Stone, Gregory G.;Chambers, Henry F.
通讯作者：
Chambers, Henry F.