## 1 Introduction  
Bacteria from the _Brucella_ genus are the causative agents of brucellosis, a neglected disease which constitutes a worldwide anthropozoonosis. _Brucella_ spp. are Gram negative alphaproteobacteria belonging to the Rhizolates order [1]. _Brucella abortus_ causes severe symptoms in mammals such as abortion in pregnant females and sterility in males. In humans, the disease is characterized by an undulant fever, also named Malta fever, and in the long term the infection leads to chronicity and symptoms such as arthritis, endocarditis and can have a fatal outcome without treatment [1]. In their hosts, _Brucellae_ invade, survive and replicate inside professional and non-professional phagocytic cells such as macrophages and trophoblasts. Inside host cells, _Brucellae_ are found in vacuoles named _Brucella_ containing vacuoles (BCVs). In the first part of their trafficking, they successively harbor markers of early and late endosomes, a phase of the trafficking in which the bacterium does not proliferate [2, 3]. This compartment presents a pH of about 4.0 to 4.5 and this acidification is essential for the successful establishment of _B. suis_ infection [4]. Afterwards, the bacteria are found in BCVs having markers of the endoplasmic reticulum, where they replicate [5]. Later in the cellular infection, bacteria are found in vacuoles characterized by autophagy-related proteins [6]. Different cellular models for in vitro study of _B. abortus_ infection of have been developed, such as the use of RAW 264.7 macrophages and HeLa epithelial cells. Some years ago, the investigations of the _B. abortus_ infection process in these models revealed that the cell cycle regulation of _B. abortus_ is linked to its virulence [2]. Indeed, for bacteria that did not segregate duplicated replication origins, the so-called G1 cells are more infectious than the S or G2 phase bacteria, i.e., bacteria currently replicating their genome or at the stage between the completion of genome replication genome and cell vision, respectively. More importantly, after internalization, bacteria remain in the G1 stage for up to 8 h, depending the host cell type, in Lamp1-positive compartments before reaching the endoplasmic reticulum where _B. abortus_ can restart its cell cycle, its DNA replication and actively proliferate [2]. During the first hours of the infection, in BCVs with endocytic markers, _B. abortus_ encounters harsh conditions such as acidic stress [7] and alkylating stress [8]. In addition, it was already proposed that _B. abortus_ has to face a starvation conditions inside host cells [9]. Starvation is the most obvious condition that could explain why _B. abortus_ is blocked at the G1 stage of the cell cycle during the first phase of its intracellular trafficking in HeLa cells and RAW 264.7 macrophages. Starvation sensing is classically involving the synthesis of (p)ppGpp (guanosine penta- or tetra-phosphate), also called alarmone. The synthesis and degradation of (p)ppGpp are catalyzed by enzymes of the RelA/SpoT family, also called Rsh enzymes. It was found that _rsh_ mutants, which should be not able to produce (p)ppGpp anymore, are strongly impaired during in vitro infection as well as during murine infection [10; 11]. The alarmone (p)ppGpp is widely used by bacteria to quickly adapt to stress conditions such as nutrient starvation. The production and accumulation of this alarmone induces pleiotropic effects, modulating transcription and translation, that commonly result in cell cycle and DNA replication delay [12; 13; 14; 15]. The ability to produce (p)ppGpp has been associated with virulence in bacterial pathogens belonging to relatively distant phylogenetic groups, such as _Legionella pneumophila_[16], _Vibrio cholerae_[17], and _Mycobacterium tuberculosis_[18]. In _Escherichia coli_, during the stringent response induced by starvation, (p)ppGpp binds directly to a site located at the interface between the \(\beta^{\prime}\) and \(\omega\) subunits of the RNA polymerase [19].