Staphylococcus aureus CcpA affects virulence determinant production and antibiotic resistance
Staphylococcus aureus CcpA affects virulence determinant production and antibiotic resistance
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DOI：
10.1128/aac.50.4.1183-1194.2006
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发表时间：
2006-04-01
影响因子：
4.9
通讯作者：
Bischoff, M
中科院分区：
文献类型：
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作者：
Seidl, K;Stucki, M;Bischoff, M
碳分解代谢蛋白A （CcpA）被认为是不同革兰氏阳性生物基因表达的主要调节因子。研究发现，金黄色葡萄球菌中ccpA同源物saCOL1786的缺失会影响生长、葡萄糖代谢和选定毒力决定因子的转录。在液体培养中，CcpA的缺失降低了生长速度和产量；然而，只要培养基中有葡萄糖存在，这种影响在指数生长阶段只是短暂的。葡萄糖的消耗和乳酸的产生延迟，而乙酸的排泄水平在突变培养中受到的影响较小，甚至更高。相比之下，在固体培养基上，Delta ccpA突变体的生长导致更小的菌落，每个菌落含有更少的CFU。CcpA的缺失通过下调agr位点的效应分子RNAIII，改变编码α -溶血素的hla和编码蛋白a的spa的转录模式，影响了金黄色葡萄球菌重要毒力因子的表达。CcpA失活显著降低了甲氧西林高度耐药金黄色葡萄球菌COLn菌株对oxacillin的耐药水平和糖肽-中间耐药金黄色葡萄球菌对teicoplanin的耐药水平。产5型荚膜多糖（CP5）的菌株Newman中CcpA的存在可在葡萄糖存在下抑制荚膜形成并降低帽操纵子转录。因此，葡萄球菌的CcpA不仅参与碳代谢的调节，而且似乎也作为毒力基因表达的调节剂发挥作用。
Carbon catabolite protein A (CcpA) is known to function as a major regulator of gene expression in different gram-positive organisms. Deletion of the ccpA homologue (saCOL1786) in Staphylococcus aureus was found to affect growth, glucose metabolization, and transcription of selected virulence determinants. In liquid culture, deletion of CcpA decreased the growth rate and yield; however, the effect was only transient during the exponential-growth phase as long as glucose was present in the medium. Depletion of glucose and production of lactate was delayed, while the level of excretion of acetate was less affected and was even higher in the mutant culture. On solid medium, in contrast, growth of the Delta ccpA mutant resulted in smaller colonies containing a lower number of CFU per colony. Deletion of CcpA had an effect on the expression of important virulence factors of S. aureus by down-regulating RNAIII, the effector molecule of the agr locus, and altering the transcription patterns of hla, encoding alpha-hemolysin, and spa, encoding protein A. CcpA inactivation markedly reduced the oxacillin resistance levels in the highly methicillin-resistant S. aureus strain COLn and the teicoplanin resistance level in a glycopeptide-intermediate-resistant S. aureus strain. The presence of CcpA in the capsular polysaccharide serotype 5 (CP5)-producing strain Newman abolished capsule formation and decreased cap operon transcription in the presence of glucose. The staphylococcal CcpA thus not only is involved in the regulation of carbon metabolism but seems to function as a modulator of virulence gene expression as well.