Die for the community: an overview of programmed cell death in bacteria

Abstract

Programmed cell death is a process known to have a crucial role in many aspects of eukaryotes physiology and is clearly essential to their life. As a consequence, the underlying molecular mechanisms have been extensively studied in eukaryotes and we now know that different signalling pathways leading to functionally and morphologically different forms of death exist in these organisms. Similarly, mono-cellular organism can activate signalling pathways leading to death of a number of cells within a colony. The reason why a single-cell organism would activate a program leading to its death is apparently counterintuitive and probably for this reason cell death in prokaryotes has received a lot less attention in the past years. However, as summarized in this review there are many reasons leading to prokaryotic cell death, for the benefit of the colony. Indeed, single-celled organism can greatly benefit from multicellular organization. Within this forms of organization, regulation of death becomes an important issue, contributing to important processes such as: stress response, development, genetic transformation, and biofilm formation.

Figure 1

Bacterial TA systems. Bacterial TA systems are composed of a toxin and an antitoxin that neutralizes its effect. They are classified on the basis of the function of the antitoxin and the composition of the TA module. In all the TA system, in response to various stimuli the antitoxin is degraded allowing the toxin to act on its target generally resulting in either bacterial growth arrest or cell death. (a) Type I: antisense RNA antitoxin binds to the mRNA encoding for the toxin blocking its translation. Loss of the unstable antisense mRNA allows transcription of the sense strand. (b) Type II: toxin and antitoxin generally transcribed in the same operon form an inactive complex. Protease-dependent degradation of the antitoxin in response to stress frees the active toxin. (c) Type III: antitoxin RNA binds and inactivates to the toxin protein. (d) Type IV: the antitoxin prevents the effect of the toxin by binding the toxin target. Again in response to stress, degradation of the antitoxin allows binding of the toxin to its target. (e) Type V: the antitoxin binds and cleaves the mRNA encoding for the toxin

Figure 2

Examples of bacterial programmed cell death. (a) Upon nutrient limitation Bacillus subtilis undergoes two fates: sporulation or non-sporulation. Death of non-sporulating cells results in nutrient release that supports sporulation. Moreover, the mother cell in the sporulating population undergoes PCD to release the mature spore. (b) Competent Streptococcus pneumonaie cells induce death of non-competent cells in order to incorporate their DNA for genetic transformation. (c) Upon nutrient starvation of Myxococcus xanthus, while a small percentage of cells remains undifferentiated and forms the peripheral rods, the majority of cells undergoes fruiting body formation. During this process, a large number of cells is lysed in order to release nutrients for the remaining cells that will differentiate into mixospores. When nutrients are available, a new colony rises from proliferation of peripheral rods cells and germination of myxospores. (d) Under stressing conditions, a part of MI cells is subjected to PCD while the remaining viable cells differentiate into MII cells. In the second phase of PCD, a part of MII cells dies releasing nutrients to feed the aerial mycelium, which is developed from branches of the remaining viable cells of MII and rises above the surface. The apical cells of the aerial hyphae differentiate into spores that can spread in the environment

Figure 3

Biofilm formation and development. Initially, planktonic cells adhere to a solid surface (1), and production of extracellular polymeric substances (EPS) stabilizes the adhered colony (2). Some of the cells undergo autolysis releasing nutrients and eDNA that promote growth and maturation of the biofilm (3). Cells are dispersed from the biofilm and can colonise other sites through three mechanisms: erosion, sloughing, and seeding dispersal (4). Seeding dispersal implicates an active process of autolysis resulting in release of single bacterial cells and cavity formation