Shedding Light on the Cell Biology of the Predatory Bacterium Bdellovibrio bacteriovorus

Abstract

Bdellovibrio bacteriovorus is a predatory bacterium that feeds upon and proliferates inside other Gram-negative bacteria. Upon entry into the periplasmic space of the prey envelope, B. bacteriovorus initiates an exquisite developmental program in which it digests the host resources and grows as a filament, which eventually divides in a non-binary manner, releasing a variable number of daughter cells. The progeny then escape from the prey ghost to encounter new victims and resume the predation cycle. Owing to its unique biology, B. bacteriovorus undoubtedly represents an attractive model to unravel novel mechanisms of bacterial cell cycle control and cellular organization. Yet, the molecular factors behind the sophisticated lifestyle of this micro-predator are still mysterious. In particular, the spatiotemporal dynamics of proteins that control key cellular processes such as transmission of the genetic information, cell growth and division remain largely unexplored. In this Perspective article, I highlight outstanding fundamental questions related to these aspects and arising from the original biology of this bacterium. I also discuss available insights and potential cell biology approaches based on quantitative live imaging techniques, in combination with bacterial genetics and biochemistry, to shed light on the intracellular organization of B. bacteriovorus in space and time.

Keywords: Bdellovibrio bacteriovorus; bacterial cell biology; cell cycle; cell division; chromosome dynamics; microscopy; polarity; predation.

FIGURE 1

Predatory lifecycle of Bdellovibrio bacteriovorus. 1. Mono-flagellated B. bacteriovorus cells swim in the attack phase. 2. Upon contact with a prey, the predator attaches to it by the non-flagellated pole via Type IVa pili (Evans et al., 2007; Mahmoud and Koval, 2010). 3. The predator squeezes through a narrow pore in the prey outer membrane and cell wall, which appears to be resealed after predator entry (Kuru et al., 2017). 4. B. bacteriovorus produces an arsenal of lytic enzymes, including peptidoglycan-degrading ones, leading to a modification of the cell wall and rounding of the prey (called bdelloplast) (Lerner et al., 2012), and digestion of the prey cytosolic content. A progressive shift in the transcriptional program of B. bacteriovorus is triggered by prey contact and sensing of undetermined intracellular prey content, and allows it to transition from the attack phase to the growth phase (Lambert et al., 2010; Karunker et al., 2013; Rotem et al., 2015). 5. B. bacteriovorus grows as a filament and presumably synthesizes an odd or even number of chromosomal copies. What determines the extent of intra-periplasmic growth and the timing of progeny release is unclear. 6. The mother cell undergoes an atypical, simultaneous non-binary division (Fenton et al., 2010b). 7. Daughter cells mature into attack phase cells before escaping in the environment. The full cycle takes ∼4 h in laboratory conditions. Rare spontaneous mutants acquire the ability to proliferate in a host-independent (HI) manner (not depicted here). A first mutation, often in a gene that may directly or indirectly regulate extrusion of the Type IVa pili required for prey attachment and invasion (Evans et al., 2007; Mahmoud and Koval, 2010; Wurtzel et al., 2010; Capeness et al., 2013), allows the cells to grow outside a prey in rich medium (Cotter and Thomashow, 1992; Roschanski et al., 2011; Capeness et al., 2013). A second mutation affecting the RNA degradosome, commits B. bacteriovorus to an irreversible HI life, in which it loses predation ability (Roschanski et al., 2011). I refer the reader to excellent publications for in-depth review of the B. bacteriovorus lifestyle (Sockett, 2009; Rotem et al., 2014; Negus et al., 2017).