## 3 Discussion
The high abundance in _SC_, in both Pi conditions, of several enzymes involved in cell wall degradation belonging to the DasR regulon (Figure S10, cluster C of [9]) indicated an autolytic degradation of the peptidoglycan cell wall in _SC_. This degradation would result in the generation of glucosamine-6P and N-acetylglucosamine-6P, the allosteric effectors of DasR [203], which impair the interaction of the latter with its operator sites allowing the expression of genes involved in N-acetylglucosamine (NAG) metabolism which is under the negative control of DaRs [204]. We propose that in _SC_ the degradation of the peptidoglycan cell wall would be triggered by nitrogen stress in order to recycle the N present in the constituents of the peptidoglycan cell wall, and would be sensed as \"cell wall stress\" inducing the expression of the SigE and SigU sigma factors (Figure 1) as well as that of the TCS vanR/vanS (sub-cluster E2) and cseB/cseC (sub-cluster B1) (Table 1). A structurally altered peptidoglycan cell wall should not be able to fulfill its osmoprotective function and this would result in osmotic stress (OsS) triggering the expression of SigH, the anti SigH SCO5244 and anti sigma factor antagonist BldG, as well as the TCS OhkA/OrrA involved in OsS response (Table 1). Consistently, electron microscopic pictures of _SL_ and _SC_ show that mycelial fragments of SC were swollen compared to those of _SL_, testifying to water entry (Figure 3B of [205]). Our study thus indicates that nitrogen, cell wall, and osmotic stresses are more intense in _SC_ than in _SL_ and are intimately linked, with nitrogen stress being the most likely initial cause of cell wall and osmotic stresses. Interestingly, the higher abundance of regulators positively controlling the expression of genes involved in the resistance to cell wall and osmotic stresses in _SC_ compared to _SL_ (14 versus 4, Table 1), signals an attempt of _SC_ to combat these stresses to maintain its cellular homeostasis. Most of these regulators have a negative impact on antibiotic biosynthesis so when these regulators are inactivated, these stresses are getting worse, and this obviously leads to a further enhancement of antibiotic production (Table 1). This observation raises the question of the nature of the links existing between these different stresses and antibiotic production. To answer this question, we propose that when the bacteria is facing a stressful situation, its attempts to combat these stresses to maintain its homeostasis are ATP consuming. The permanence and intensity of these stresses would possibly overwhelm these resistance systems leading to further ATP consumption to face the detrimental consequences of the latter, resulting in ATP depletion. Such ATP depletion would trigger the activation of the oxidative metabolism that, coupled with respiration, constitutes an attempt to restore the cellular energetic balance but also generates OxS [9; 10; 12]. OxS was proposed to be an important trigger for the expression of ACT in _SC_[9; 12] since ACT was shown to bear an anti-oxidant function [8]. The anti-oxidant function of ACT is thought to be due to its ability to capture excess electrons of ROS and NOS thanks to its quinone groups [206]. Furthermore, since the onset of ACT biosynthesis was shown to coincide with an abrupt drop of the ATP content of the bacteria [10], ACT might also be able to capture electrons of the respiratory chain, reducing its activity and thus the generation of ATP. ACT would thus have both anti-respiratory and anti-oxidant functions. The two other antibiotics produced by _SC_, CDA [207], and RED [208] are known to alter the permeability of the cellular membrane and this might lead to the dissipation of the H+ gradient and thus to a reduction of respiratory activity and ATP generation. The function of these three molecules would be to reduce the excessive respiratory activity of _SC_ in order to limit its detrimental effects such as OxS as well as the generation of ATP when Pi is scarce.