Claushuis, B. | bioRxiv Science

bioRxiv2021

Generating heterokaryotic cells via bacterial cell-cell fusion

Cell-cell fusion is fundamentally important for tissue repair, virus transmission, and genetic recombination, among other functions. Fusion has been mainly studied in eukaryotic cells and lipid vesicles, while cell-cell fusion in bacteria is less well characterized, due to the cell wall acting as a fusion-limiting barrier. Here we use cell wall-deficient bacteria to investigate the dynamics of cell fusion in bacteria that replicate without their cell wall. Stable, replicating cells containing differently labeled chromosomes were successfully obtained from fusion. We find that the rate of cell-cell fusion depends on the fluidity of cell membranes. Furthermore, we show that not only the efficiency but also the specificity of cell-cell fusion can be controlled via a pair of synthetic membrane-associated lipopeptides. Our results provide a molecular handle to understand and control cell-cell fusion to generate heterokaryotic cells, which was an important step in the evolution of protocells and of increasing importance for the design of synthetic cells.

microbiology↗

bioRxiv2020

Mutational meltdown of microbial altruists in Streptomyces coelicolor colonies

In colonies of the filamentous multicellular bacterium Streptomyces coelicolor, a sub-population of cells arise that hyper-produce metabolically costly antibiotics, resulting in division of labor that maximizes colony fitness. Because these cells contain large genomic deletions that cause massive reductions to individual fitness, their behavior is altruistic, much like worker castes in social insects or somatic cells in multicellular organisms. To understand the reproductive and genomic fate of these mutant cells after their emergence, we use experimental evolution by serially transferring populations via spore-to-spore transfer for 25 cycles, reflective of the natural mode of bottlenecked transmission for these spore-forming bacteria. We show that, in contrast to wild-type cells, altruistic mutant cells continue to significantly decline in fitness during transfer while they delete larger and larger fragments from their chromosome ends. In addition, altruistic mutants acquire a roughly 10-fold increase in their base-substitution rates possibly due to mutations in genes for DNA replication and repair. Ecological damage, caused by reduced sporulation, coupled with irreversible DNA damage due to point mutations and deletions, leads to an inevitable and irreversible type of mutational meltdown in these cells. Taken together, these results suggest that the altruistic cells arising in this division of labor are analogous to reproductively sterile castes of social insects.

evolutionary biology↗