Bet-hedging in bacteriocin producing Escherichia coli populations: the single cell perspective

Abstract

Production of public goods in biological systems is often a collaborative effort that may be detrimental to the producers. It is therefore sustainable only if a small fraction of the population shoulders the cost while the majority reap the benefits. We modelled this scenario using Escherichia coli populations producing colicins, an antibiotic that kills producer cells’ close relatives. Colicin expression is a costly trait, and it has been proposed that only a small fraction of the population actively expresses the antibiotic. Colicinogenic populations were followed at the single-cell level using time-lapse microscopy, and showed two distinct, albeit dynamic, subpopulations: the majority silenced colicin expression, while a small fraction of elongated, slow-growing cells formed colicin-expressing hotspots, placing a significant burden on expressers. Moreover, monitoring lineages of individual colicinogenic cells showed stochastic switching between expressers and non-expressers. Hence, colicin expressers may be engaged in risk-reducing strategies—or bet-hedging—as they balance the cost of colicin production with the need to repel competitors. To test the bet-hedging strategy in colicin-mediated interactions, competitions between colicin-sensitive and producer cells were simulated using a numerical model, demonstrating a finely balanced expression range that is essential to sustaining the colicinogenic population.

Plastic responses to competition: Does bacteriocin production increase in the presence of nonself competitors?

“…Consequently, only a small proportion of the producer population is actively engaged in bacteriocin production and release at a given time. In Escherichia coli , this frequency has been estimated to range between 0.5% and 9% using GFP reporter strains linked to bacteriocin promoters (Bayramoglu et al., ; Mulec et al., ). While similar estimates for the frequency of cells actively producing bacteriocin remain to be determined for the natural isolates of Xenorhabdus spp., our functional assays clearly show no evidence in support of the hypothesis that bacteriocin production increases in the presence of nonself competitors.…”

“…Consequently, only a small proportion of the producer population is actively engaged in bacteriocin production and release at a given time. In Escherichia coli, this frequency has been estimated to range between 0.5% and 9% using GFP reporter strains linked to bacteriocin promoters (Bayramoglu et al, 2017;Mulec et al, 2003).…”

The Evolution of Mass Cell Suicide in Bacterial Warfare

“…We followed the production of the colicin E2 toxin and its cognate immunity protein (Figure 1A) using a reporter plasmid that expresses green fluorescent protein ( gfp ) from the native colicin E2 promoter [9] (pUA66-PcolE2:: gfp , Figure 1B-D). This construct, like others previously studied [10,12,22,23], allows one to identify cells that may be on their way to cell suicide via lysis [1–3]. However, it is not sufficient to follow the full behaviour, as the self-lysis process is dependent on the expression of the lysis gene in the colicin operon [18,24], which is subject to several additional layers of regulation at both the transcriptional and post-transcriptional level [17,25–28].…”

“…When a colicin producing strain is growing alone, the colicin operon is typically only expressed in a small fraction of the population [9–15]. Expression can be upregulated by DNA damage as the colicin operon is regulated by the SOS response pathway [14,16,17], which is often done artificially via the addition of DNA-damaging agents such as mitomycin C [12,14,16,18,19]. However, many natural colicins also damage DNA, and these too have been shown to upregulate colicin production in targeted cells [9,20], an example of competition sensing [21] (Figure 1).…”

The Role of Background Bacteria in Preventing the Isolation and Detection of Shigella and STEC in Foods and Novel MuSIC ddPCR Method to Improve STEC Detection in the Presence of Background Bacteria

“…Expression of the lysis gene is tightly controlled, and not all cells in a population produce the lysis and colicin genes at the same time. In a culture, about 0.1% of the cells produce colicin and cause lysis under normal conditions and this is increased to 3% during nutrient starvation and 50% after SOS response (Bayramoglu et al, 2017). The immunity gene is continuously being expressed at small levels so that a bacterium closely related to the cell releasing colicin can be protected (Ghazaryan et al, 2014).…”