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Spore formation by the bacterium Bacillus subtilis is an elaborate developmental process that is triggered by nutrient limitation. Here we report that cells that have entered the pathway to sporulate produce and export a killing factor and a signaling protein that act cooperatively to block sister cells from sporulating and to cause them to lyse. The sporulating cells feed on the nutrients thereby released, which allows them to keep growing rather than to complete morphogenesis. We propose that sporulation is a stress-response pathway of last resort and that B. subtilis delays a commitment to spore formation by cannibalizing its siblings.
Some microorganisms respond to nutritional limitation by entering a resting state in which they remain inactive for an extended time. Bacillus subtilis produces a robust resting cell, the endospore, that can remain dormant for many years. Endospore formation is an elaborate and energy intensive process that requires several hours to complete (1-4). If during this period nutrients were once again to become plentiful, the sporulating cells would be at a disadvantage relative to cells able to resume growth rapidly. Thus, bacteria could be expected to delay spore formation until forced to do so by prolonged depletion of nutrients. Here we present evidence that cells that have entered the pathway to sporulate delay development by killing their siblings and feeding on the nutrients thereby released. Cannibalism is mediated by an extracellular killing factor and a novel intercellular signaling protein that act cooperatively to cause cell death and impede sporulation.
Entry into sporulation is governed by the regulatory protein Spo0A (5). While building mutants of genes under the control of Spo0A (6), we discovered two operons (Fig. 1A) that are strongly induced at the start of sporulation (fig. S1) and in which mutations accelerated spore formation (Fig. 1, B and C, and fig. S2). We refer to these operons as skf for sporulation killing factor and sdp for sporulation delaying protein.
Clues that the eight-gene skf operon directs the production of an exported killing factor came from the similarity of its gene products to proteins involved in the production of peptide antibiotics (7-9). The first gene, skfA, encodes a small peptide, a characteristic of operons involved in the production of peptide antibiotics (7). The product of...