## 2 The Csr Network  
### CsrA Is a Global Regulator  
The first component of the Csr network was described in 1993 in _E. coli_[8]. In a screen to identify genes involved in glycogen biosynthesis by transposon mutagenesis, the group of [PERSON] identified the _csrA_ gene as encoding a negative regulator of glycogen accumulation. Subsequently, it was shown that CsrA is a 61 amino acid protein that regulates translation by binding to mRNA targets [9, 10]. In addition to its implication in glycogen synthesis regulation, CsrA regulates central carbon metabolism. The observation that expression of the _pckA_ gene, using a _pckA::lacZ_ translational fusion, was increased in the _csrA::kan_ mutant provided the first evidence of _csrA_ implication in gluconeogenesis regulation [8]. _pckA_ encodes phosphoenolpyruvate carboxykinase, a key regulatory enzyme in this pathway. Later on, in a study evaluating glycolysis and gluconeogenesis enzyme activities, gene expression and metabolites, it was inferred that CsrA has a global positive effect on glycolysis and a global negative effect on gluconeogenesis [11]. Accordingly, glucose consumption and extracellular levels of acetate were shown to be reduced in _csrA_ depletion conditions [12]. Expression of the _acs_ (acetyl-CoA synthetase) and _aceA_ (isocitrate lyase) is positively regulated by CsrA [13]. In addition, ATP level is reduced while AMP and ADP levels are increased, indicating a lower energy charge [11]. In a recent paper, global changes upon _csrA_ depletion (using overexpression of the sRNA CsrB, see below) were monitored using proteomics and metabolomics approaches [12]. This study confirmed that central carbon metabolism is generally affected in these conditions. Intermediates of glycolysis, phosphoenolpyruvate (PEP), acetyl-CoA and intermediates of the glyoxylate shunt are accumulating. Amino acid and fatty acid metabolisms are also impacted [12]. In species other than _E. coli_, such as Salmonella_, deletion of _csr.A_ was also shown to affect metabolism, _i.e._, maltose transport, ethanolamine utilization, and propenediol metabolism [14]. Thus, a defect in _csr.A_ drastically alters carbon flux distribution. Effects on gene expression have been shown for a few enzymes, raising the possibility that most of the effects might be consequences of accumulation of specific intermediates that modify enzyme activity and redirect carbon into other metabolites. In addition to its role in central carbon metabolism, CsrA controls the switch between sessile (biofilm) and planktonic lifestyle [15]. The _csr.A:kan_ mutation increases adherence [8] while it drastically reduces motility. Several direct regulations mediated by CsrA are involved in this switch. CsrA negatively regulates _pgaABCD_ expression which contributes to \(\beta\)-1,6-\(N\)-acetyl-d-glucosamine (PGA) synthesis [16], an exopolysaccharideacharide involved in adhesion [17]. CsrA positively regulates _flhDC_ expression, encoding the flagellar master regulator [18, 19]. In addition, the level of c-di-GMP, a signaling molecule that notably controls biofilm formation and motility, is affected in the _csr.A:kan_ mutant (for review, see [20]). CsrA negatively regulates the expression of seven genes encoding proteins with GGDEF and/or EAL domains (responsible for diguanylate cyclase and phosphodiesterase activities, respectively) [21]. CsrA is also involved in bacterial interactions with animal and plant hosts (for reviews, see [22, 23, 24]). For example, CsrA is involved in _Salmonella typhimurium_ invasion of epithelial cells and survival inside macrophages [25]. The CsrA homologues in the _Pectobacterium_ genus (RsmA) play a crucial role in infection and colonization of host plants [26]. In the opportunistic human pathogen _P. aeruginosa_, RsmA is involved in the control of a wide variety of processes involved in pathogenesis, such as hydrogen cyanide synthesis [27], type IV pili expression [28], quorum sensing [29] as well as type VI and type III secretion systems [28].