On the link between cell cycle and infection of the Alphaproteobacterium Brucella abortus

Abstract

Bacteria of the Brucella genus are responsible for brucellosis, a worldwide zoonosis. These bacteria are known to have a peculiar intracellular trafficking, with a first long and non-proliferative endosomal stage and a second proliferation stage, often associated with its localization of the bacteria in the endoplasmic reticulum (ER). However, the status of the bacterial cell cycle during the non-proliferative phase was still unknown. In a recent study [Nat. Communic. 5:4366], we followed the cell cycle of B. abortus in culture and inside the host cells. In culture, B. abortus initiates the replication of its large chromosome before the small chromosome. The origin and terminator regions of these two chromosomes display distinct localization and dynamics within B. abortus. In HeLa cells and RAW264.7 macrophages, the bacteria in G1 (i.e. before the initiation of chromosomes replication) are preferentially found during the endosomal stage of the infection. During this period, growth is also arrested. The cell cycle arrest and resume during the B. abortus trafficking in host cell suggest that like the model Alphaproteobacterium Caulobacter crescentus, these bacteria are able to block their cell cycle at the G1 phase when starvation is sensed.

Keywords: Brucella; Caulobacter; bacterial cell cycle; cellular infection; intracellular trafficking.

Figure 1. FIGURE 1: Comparison of B. abortus and C. crescentus cell cycle controls according to their lifestyle.

The B. abortus replication origins of chromosome I (oriI) and chromosome II (oriII) are shown in red and green, respectively. The replication origin of the unique chromosome of C. crescentus (oriC) is shown in red. B. abortus duplicates its oriI before replication an segregation of its oriII. Inside host cells, at 15 min until 6 h post-infection (PI), the bacteria are mainly in G1 since unique spots of oriI and oriII are observed. This G1 arrest is similar to the G1 arrest observed in swarmer cells of C. crescentus. Thanks to their unique polar flagellum, the swarmer cells are able to move from an original niche to a new niche, in which nutrients are more abundant. In the original niche, the stalked cells are immobilized because they stick to a substrate, thanks to the holdfast at the end of their stalk (small white rectangle). In the case of B. abortus, the ER could be considered as a new niche in which nutrients are abundant, since this pathogen massively replicates in this organelle.