The Evolution of Mass Cell Suicide in Bacterial Warfare
Authors: Kevin R Foster
Elisa T Granato
Journal: Current Biology (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Escherichia coli; bacteriocins; cell suicide; colicins; collective behavior
Affiliations: Department of Zoology, University of Oxford, 11a Mansfield Road, OX1 3SZ Oxford, UK; Department of Biochemistry, University of Oxford, 3 South Parks Road, OX1 3QU Oxford, UK. Electronic address: .

Abstract:  Behaviors that cause the death of an actor are typically strongly disfavored by natural selection, and yet many bacteria undergo cell lysis to release anti-competitor toxins [1-5]. This behavior is most easily explained if only a small proportion of cells die to release toxins and help their clonemates, but the frequency of cells that actually lyse during bacterial warfare is unknown. The challenge is finding a way to distinguish cells that have undergone programmed suicide from those that were simply killed by a competitor's toxin. We developed a two-color fluorescence reporter assay in Escherichia coli to overcome this problem. This revealed conditions where nearly all cells undergo programmed lysis. Specifically, adding a DNA-damaging toxin (DNase colicin) from another strain induced mass cell suicide where ∼85% of cells lysed to release their own toxins. Time-lapse 3D confocal microscopy showed that self-lysis occurs locally at even higher frequencies (∼94%) at the interface between toxin-producing colonies. By exposing E. coli that do not perform lysis to the DNase colicin, we found that mass lysis occurs when cells are going to die anyway from toxin exposure. From an evolutionary perspective, this renders the behavior cost-free as these cells have zero reproductive potential. This helps to explain how mass cell suicide can evolve, as any small benefit to surviving clonemates can lead to this retaliatory strategy being favored by natural selection. Our findings have parallels to the suicidal attacks of social insects [6-9], which are also performed by individuals with low reproductive potential. 

Retracted: No

PubPeer comments:
 The following are my opinions, and the readers are encouraged to decide for themselves without any bias. The best hope is to initiate discussions and to engage alternate views. Science all the way! This paper is a technologically sound work. However, I take exception to the interpretation of the results in an evolutionary perspective. The results are based on pitting two strains (each containing a different colicin encoding plasmid) against each other. They observed a massive death of one strain which is dubbed as u2018suicideu2019. This is a troublesome interpretation or forceful fitting of altruistic death like phenomenon observed in complex social organisms (e.g. Bees). Typically, altruistic death is observed in individuals with no reproductive potential (the worker bees). The authors have shown that the death of one strain is caused by the lysis protein encoded by the in-house plasmid and hence refer it to as suicide! They further summarize the study as, u201cSelf-lysis makes evolutionary sense as cells will die anyway from competitorsu2019 toxins.u201d From the gene centred view, these interpretations are faulty. While the observations could be correct, the authors must have explored alternate explanations as well. 1. Self: Suicide is self-inflicted death. The competitor strain is almost a clone except for the dispensable plasmid? The plasmid is not an inherent part of the bacterial genome. One should have considered all propagating entities (genomes and plasmids) as individual players. In that view, the experiments are actually between the plasmids that have parasitized different bacterial cells. 2. Evolutionary sense: The plasmids encode the colicin gene, immunity gene and the lysis gene. The genomes (as cells) are limited to harbouring the plasmids. Thence, the observations should be attributed solely to the plasmids alone and not applicable to the cells as a trait. It is not suicide by the cells but genocide by the plasmids! 3. u201cSelf-lysis makes evolutionary sense as cells will die anyway from competitorsu2019 toxins.u201d: This seems to overstate the capabilities of bacteria. It is attributing foresight to bacteria. In this context, the bacteria are not sensing the attack from the competing strain specifically. The focal strain or competitor strains do not have specialized mechanisms to perceive specific stress such as a receptor for the incoming colicin. Instead, the focal strain is responding to the DNA damage. Irrespective of the cause, the response of cell lysis will be similar as long as there is DNA damage. Cell lysis will occur even if the DNA is damaged by the mitomycin or UV light. Moreover, the in-house plasmid is the cause for the cell lysis. Hence, massive u2018suicideu2019 is not a strategy of the focal strain, but rather, it is u2018genocideu2019 mediated by the in-house plasmid. 4. The reproductive potential of bacteria in relation to suicide. In altruistic death in complex organisms, the individuals with low or no reproductive potential are usually the ones that die defending the rest of the populationu2014generally irreversible sterility on a population scale. In contrast, the reproductive potential in bacteria is dynamic and is a function of the prevailing conditions. Unlike in bees or other examples, the reproductive potential of each bacterium in a population is reversible. The bacterial SOS response (u201cSave Our Soulsu201d) is an evolved survival strategy as the bacterium attempts to regain the reproductive potential. The observations of Granato and Foster could mean that damaged cells are more prone to lysis and should not be equated with the low reproductive potential of higher organisms as in the case of altruism. In a way, it makes evolutionary sense for the plasmid to abandon the damaged cell for a healthier cell! 5. The propagation games: One should have considered each of the autonomously replicating entity as a component in these competitions. In this study, the bacterial genomes and the two plasmids are the competitors. In the whole cycle of events that include invasion, proliferation, cell lysis and plasmid release, there is a net loss of genomes relative to the plasmids. What would it mean for the plasmid at all? Because the in-house plasmid would eventually kill most of the colicin encoding plasmid harbouring bacteria, we should appreciate that the plasmids are the winners, and bacteria are a medium of plasmid propagation. 6. How is the bacterial death due to plasmid (lysis encoding) different from the bacterial death caused by a temperate bacteriophage? There are more similarities than differences in the killing of the bacterial cell (the host to the parasites; plasmids and phages). All the observations must have been viewed with genes and replicons as the focus. Thanks , 
 u201cIf we are uncritical, we shall always find what we want: we shall look for, and find, confirmations, and we shall look away from, and not see, whatever might be dangerous to our pet theories.u201d Karl Raimund Popper, 1957. ,