CcpA coordinates central metabolism and biofilm formation in Staphylococcus epidermidis.
CcpA coordinates central metabolism and biofilm formation in Staphylococcus epidermidis.
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DOI：
10.1099/mic.0.051243-0
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发表时间：
2012-07
期刊：
影响因子：
1.5
通讯作者：
M. Sadykov;T. Hartmann;Theodoric A. Mattes;M. Hiatt;N. Jann;Yefei Zhu;N. Ledala;R. Landmann;M. Herrmann;H. Rohde;M. Bischoff;G. Somerville
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文献类型：
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作者：
M. Sadykov;T. Hartmann;Theodoric A. Mattes;M. Hiatt;N. Jann;Yefei Zhu;N. Ledala;R. Landmann;M. Herrmann;H. Rohde;M. Bischoff;G. Somerville
表皮葡萄球菌是一种机会性细菌，其感染通常涉及在植入的生物材料上形成生物膜。In S.在表皮葡萄球菌中，促进细菌粘附在生物膜中的外泌多糖是多糖细胞间粘附素（PIA），其合成需要在细胞间粘附素操纵子（icaADBC）内编码的酶。在体外，S.表皮细胞生物膜通过抑制三羧酸（TCA）循环活性的条件，例如在含有葡萄糖的培养基中生长而增强。在许多革兰氏阳性菌中，响应于葡萄糖的TCA循环基因的阻遏是通过分解代谢物控制蛋白A（CcpA）完成的。CcpA是GalR-LacI阻遏物家族的一员，它介导碳代谢产物的阻遏，这使我们推测S.表皮生物膜的形成是由TCA循环的CcpA依赖性抑制间接调节的。为了验证这一假设，在菌株1457和1457-acnA中构建ccpA缺失突变体，并评估对TCA循环活性、生物膜形成和毒力的影响。正如预期的那样，缺失ccpA解除了TCA循环活性并抑制了生物膜形成;然而，ccpA缺失对icaADBC转录仅具有适度的影响。令人惊讶的是，菌株1457-acnA（其TCA循环是失活的并且其中icaADBC转录被去阻遏的菌株）中ccpA的缺失强烈抑制icaADBC转录。这些观察结果表明，CcpA是生物膜形成和icaADBC转录的正效应子和TCA循环活性的阻遏物。
Staphylococcus epidermidis is an opportunistic bacterium whose infections often involve the formation of a biofilm on implanted biomaterials. In S. epidermidis, the exopolysaccharide facilitating bacterial adherence in a biofilm is polysaccharide intercellular adhesin (PIA), whose synthesis requires the enzymes encoded within the intercellular adhesin operon (icaADBC). In vitro, the formation of S. epidermidis biofilms is enhanced by conditions that repress tricarboxylic acid (TCA) cycle activity, such as growth in a medium containing glucose. In many Gram-positive bacteria, repression of TCA cycle genes in response to glucose is accomplished by catabolite control protein A (CcpA). CcpA is a member of the GalR-LacI repressor family that mediates carbon catabolite repression, leading us to hypothesize that catabolite control of S. epidermidis biofilm formation is indirectly regulated by CcpA-dependent repression of the TCA cycle. To test this hypothesis, ccpA deletion mutants were constructed in strain 1457 and 1457-acnA and the effects on TCA cycle activity, biofilm formation and virulence were assessed. As anticipated, deletion of ccpA derepressed TCA cycle activity and inhibited biofilm formation; however, ccpA deletion had only a modest effect on icaADBC transcription. Surprisingly, deletion of ccpA in strain 1457-acnA, a strain whose TCA cycle is inactive and where icaADBC transcription is derepressed, strongly inhibited icaADBC transcription. These observations demonstrate that CcpA is a positive effector of biofilm formation and icaADBC transcription and a repressor of TCA cycle activity.