The bactericidal activity of phlorotannins from brown algae against food-borne pathogenic bacteria (25 strains), methicillin-resistant Staphylococcus aureus (MRSA) (nine strains) and Streptococcus pyogenes (one strain) was examined and compared with that of catechins. In addition, the effect of the oral administration of phlorotannins on mice was investigated. Phlorotannins, which are oligomers of phloroglucinol, were extracted from thalli of the brown alga Ecklonia kurome and prepared by silicic acid chromatography. The bactericidal activity of polyphenols was determined using a broth microdilution method. Of the bacteria tested, Campylobacter spp. were the most susceptible to the phlorotannins. The MBCs of the crude phlorotannins, dieckol and 8,8'-bieckol (hexamers), and that of epigallocatechin gallate (EGCG) against Campylobacter jejuni were 50 mg/L, 0.03 micromol/mL and 0.03 micromol/mL, respectively. On the whole, the bactericidal effects of the phlorotannins were more pronounced than those of the catechins. The phlorotannins were as effective against MRSA as against the other bacteria tested. At twice the MBCs, all Vibrio parahaemolyticus were killed within 0.5-2 h. However, at the same concentration, catechins showed little bactericidal activity within 4 h. No effect on mice was observed with oral administration of the phlorotannins under the conditions tested.

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SummaryCell-cell heterogeneity can facilitate lineage choice during embryonic development because it primes cells to respond to differentiation cues. However, remarkably little is known about the origin of heterogeneity or whether intrinsic and extrinsic variation can be controlled to generate reproducible cell type proportioning seen in vivo. Here, we use experimentation and modeling in D. discoideum to demonstrate that population-level cell cycle heterogeneity can be optimized to generate robust cell fate proportioning. First, cell cycle position is quantitatively linked to responsiveness to differentiation-inducing signals. Second, intrinsic variation in cell cycle length ensures cells are randomly distributed throughout the cell cycle at the onset of multicellular development. Finally, extrinsic perturbation of optimal cell cycle heterogeneity is buffered by compensatory changes in global signal responsiveness. These studies thus illustrate key regulatory principles underlying cell-cell heterogeneity optimization and the generation of robust and reproducible fate choice in development.

In cell culture, genetically identical cells often exhibit heterogeneous behavior, with only ‘lineage primed’ cells responding to differentiation inducing signals. It has recently been proposed that such heterogeneity exists during normal embryonic development to allow position independent patterning based on ‘salt and pepper’ differentiation and sorting out. However, the molecular basis of lineage priming and how it leads to reproducible cell type proportioning are poorly understood. To address this, we employed a novel forward genetic approach in the model organism Dictyostelium discoideum. These studies reveal that the Ras-GTPase regulator gefE is required for normal lineage priming and salt and pepper differentiation. This is because Ras-GTPase activity sets the intrinsic response threshold to lineage specific differentiation signals. Importantly, we show that although gefE expression is uniform, transcription of its target, rasD, is both heterogeneous and dynamic, thus providing a novel mechanism for heterogeneity generation and position-independent differentiation.DOI: http://dx.doi.org/10.7554/eLife.01067.001

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