## 6 Metabolic Regulation of the HrpG/HrpX Regulon
Similar phenotypes were observed upon deletion of transcriptional regulator _dkSA_[74], which is associated with alteration of the affinity of the RNA polymerase to (p)ppGpp [75] (Figure 2). These observations suggest that _hrp_ gene expression is regulated by internal levels of (p)ppGpp that are presumably controlled by nutrient limitation. Most plant-mimicking media induce _hrp_ gene expression to a significantly higher level compared with minimal media such as M9, which is more limited in nutrients [69]. Taken together, it seems that starvation-induced stringent response is not sufficient to induce the HrpG/HrpX regulon. Carbon sensing plays an essential role in the activation or suppression of the _hrp_ regulon. Utilization of sucrose and fructose as the main carbon source strongly induces _hrp_ gene expression in _Xeu_, whereas such genes are not responsive to other sugars such as xylose and mannitol [69]. On the other hand, xylose appears to be a key inducer of _hrp_ gene expression in _Xoo_[70]. Further studies have identified that the contribution of xylose to _hrp_ gene expression in _Xoo_ occurs downstream of the transcriptional regulation of _hrpX_. [PERSON] and [PERSON] reported that sucrose, galactose, fructose, and glucose promote the up-regulation of _hrpG_ and _hrpX_[76, 77], whereas structural components of the T3 SS are transcriptionally upregulated specifically in the presence of xylose, presumably by stabilizing the HrpX protein [76] (Figure 2). Accordingly, deletion of the xylose responsive Lacl-like transcriptional repressor _xylR_ resulted in higher accumulation of HrpX protein and enhanced expression of T3 SS structural genes as well [78] (Figure 2). The Clp/CRP transcriptional regulator is associated with cAMP-mediated carbon regulation in proteobacteria [79]. Disruption of _clp_ in several _Xanthomonas_ spp. abolished virulence and exoenzyme production [80, 81, 82, 83]. A few studies suggested that Clp is indirectly associated with _hrp_ gene regulation. For instance, _Xcc clp_ mutant displays reduced expression of several _effectors_ and _hrp_ genes through the Tett transcriptional regulator FhrR [81] (Figure 2). A _hrrR_ homolog is absent in many _Xanthomonas_ species, such as _Xeu_, _Xoo_, _Xcci_, and _Xcitri_ pv. _glycines_ (_Xcg_). Indeed, a second transcriptome-based study conducted in _Xcg_ did not identify _Clp_-dependent _hrp_ regulation [83]. However, the study found that _clp_ is regulated by HrpG and HrpX in _Xcg_, further establishing that Clp and Hrp regulation are somewhat interconnected [83] (Figure 2). Negative metabolic regulation by specific carbonic compounds was reported in numerous studies. Supplementation of XVM1 with TCA cycle-associated carbonic acids citrate, succinate, and pyruvate represses _hrp_ gene expression in _Xeu_[69]. Exogenous supplementation of long-chain fatty acids such as oleic and myristic acids represses _hrp_ gene expression in _Xcci_[84]. This suppression was linked to the TetR-family transcriptional repressor TfmR that directly regulates fatty acid beta-oxidation genes in response to long-chain fatty acids [84] (Figure 2). Accordingly, disruption of _tfmR_ resulted in significantly reduced virulence in citrus plants that can be partially complemented by overexpression of _hrpG_[84].