Transcriptional profiling of a Staphylococcus aureus clinical isolate and its isogenic agr and sarA mutants reveals global differences in comparison to the laboratory strain RN6390
Transcriptional profiling of a Staphylococcus aureus clinical isolate and its isogenic agr and sarA mutants reveals global differences in comparison to the laboratory strain RN6390
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DOI：
10.1099/mic.0.29033-0
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发表时间：
2006-10-01
期刊：
影响因子：
2.8
通讯作者：
Smeltzer, Mark S.
中科院分区：
文献类型：
--
作者：
Cassat, James;Dunman, Paul M.;Smeltzer, Mark S.
金黄色葡萄球菌毒力因子的产生受到复杂的调控回路的控制。大多数旨在定义这些调控网络的研究都集中在菌株NCTC 8325的衍生物上，最值得注意的是RN 6390。然而，所有NCTC 8325衍生物，包括RN 6390，在rsbU中具有11 bp缺失。这种缺失使得NCTC 8325衍生物天然缺乏σ-因子-B。最近的研究表明，与临床分离株相比，RN 6390在生物膜形成方面也有缺陷，生物膜形成是一个对发病机制和抗微生物耐药性都很重要的过程。基于这些考虑，作者进行了基因组规模的转录谱分析，比较RN 6390与强毒rsbU阳性临床分离株UAMS-1。结果显示RN 6390和UAMS-1之间的表达模式在全基因组范围内存在显著差异，并表明UAMS-1的整体转录谱与促进定植和生物膜形成的因子的表达有关。相比之下，RN 6390的转录谱受到RNAIII表达的严重影响，导致以增加外蛋白的产生和降低形成生物膜的能力为特征的表型。当将UAMS-1的转录谱与其同基因sarA和agr突变体的转录谱进行比较时，相对于UAMS-1，RN 6390中agr的影响更大也是显而易见的。具体而言，结果表明，与NCTC 8325衍生物相比，与sarA相比，agr在UAMS-1中基因表达的整体调控中发挥有限的作用。此外，通过定义生物膜阳性临床分离株中的sarA调节子，并将结果与定义相同菌株中生物膜相关基因表达模式的转录谱实验进行比较，作者鉴定了一种也在生物膜中诱导的sarA调节操纵子（alsSD），并证明alsSD突变导致形成生物膜的能力降低。
The production of Staphylococcus aureus virulence factors is under the control of complex regulatory circuits. Most studies aimed at defining these regulatory networks have focused on derivatives of the strain NCTC 8325, most notably RN6390. However, all NCTC 8325 derivatives, including RN6390, possess an 11 bp deletion in rsbU. This deletion renders NCTC 8325 derivatives naturally sigma-factor-B deficient. Recent studies have shown that RN6390 is also deficient, in comparison to clinical isolates, with respect to biofilm formation, a process which is important for both pathogenesis and antimicrobial resistance. Based on these considerations, the authors carried out genome-scale transcriptional profiling, comparing RN6390 with the virulent rsbU-positive clinical isolate UAMS-1. The results revealed significant genome-wide differences in expression patterns between RN6390 and UAMS-1, and suggested that the overall transcriptional profile of UAMS-1 is geared toward expression of factors that promote colonization and biofilm formation. In contrast, the transcriptional profile of RN6390 was heavily influenced by RNAIII expression, resulting in a phenotype characterized by increased production of exoproteins, and decreased capacity to form a biofilm. The greater influence of agr in RN6390 relative to UAMS-1 was also evident when the transcriptional profile of UAMS-1 was compared with that of its isogenic sarA and agr mutants. Specifically, the results indicate that, in contrast to NCTC 8325 derivatives, agr plays a limited role in overall regulation of gene expression in UAMS-1, when compared with sarA. Furthermore, by defining the sarA regulon in a biofilm-positive clinical isolate, and comparing the results with transcriptional profiling experiments defining biofilm-associated gene expression patterns in the same strain, the authors identified a sarA-regulated operon (alsSD) that is also induced in biofilms, and demonstrated that mutation of alsSD results in reduced capacity to form a biofilm.