The emergence of antibiotic tolerance (prolonged survival against exposure) in natural bacterial populations is a major concern. Since it has been studied primarily in isogenic populations, we do not yet understand how ecological interactions in a diverse community impact the evolution of tolerance. To address this, we studied the evolutionary dynamics of a synthetic bacterial community composed of two interacting strains. In this community, an antibiotic-resistant strain protected the other, susceptible strain by degrading the antibiotic ampicillin in the medium. Surprisingly, we found that in the presence of antibiotics, the susceptible strain evolved tolerance. Tolerance was typified by an increase in survival as well as an accompanying decrease in the growth rate, highlighting a trade-off between the two. A simple mathematical model explained that the observed decrease in the death rate, even when coupled with a decreased growth rate, is beneficial in a community with weak protective interactions. In the presence of strong interactions, the model predicted that the trade-off would instead be detrimental, and tolerance would not emerge, which we experimentally verified. By whole genome sequencing the evolved tolerant isolates, we identified two genetic hot spots which accumulated mutations in parallel lines, suggesting their association with tolerance. Our work highlights that ecological interactions can promote antibiotic tolerance in bacterial communities, which has remained understudied.

An elaborate network of sRNA-mRNA interactions controls the pathogenicity of enteropathogenic Escherichia coli. , Small RNAs (sRNAs) exert their regulation posttranscriptionally by base pairing with their target mRNAs, often in association with the RNA chaperone protein Hfq. Here, integrating RNA-seq–based technologies and bioinformatics, we deciphered the Hfq-mediated sRNA-target interactome of enteropathogenic Escherichia coli (EPEC). The emerging network comprises hundreds of sRNA-mRNA pairs, including mRNAs of virulence-associated genes interacting with known sRNAs encoded within the core genome, as well as with newly found sRNAs encoded within pathogenicity islands. Some of the sRNAs affect multiple virulence genes, suggesting they function as hubs of virulence control. We further analyzed one such sRNA hub, MgrR, and one of its targets identified here, the major virulence-associated chaperon, cesT . We show that MgrR adjusts the level of EPEC cytotoxicity via regulation of CesT expression. Our results reveal an elaborate sRNA-mRNA interactome controlling the pathogenicity of EPEC and reinforce a role for sRNAs in the control of pathogen-host interaction.

We describe a recent approach for distinguishing between stochastic and deterministic sources of variability, focusing on the mammalian cell cycle. Variability between cells is often attributed to stochastic noise, although it may be generated by deterministic components. Interestingly, lineage information can be used to distinguish between variability and determinism. Analysis of correlations within a lineage of the mammalian cell cycle duration revealed its deterministic nature. Here, we discuss the sources of such variability and the possibility that the underlying deterministic process is due to the circadian clock. Finally, we discuss the “kicked cell cycle” model and its implication on the study of the cell cycle in healthy and cancerous tissues.

Telomerase synthesizes telomeric DNA by copying a short template sequence within its telomerase RNA component. We delineated nucleotides and base-pairings within a previously mapped central domain of the Saccharomyces cerevisiae telomerase RNA (TLC1) that are important for telomerase function and for binding to the telomerase catalytic protein Est2p. Phylogenetic comparison of telomerase RNA sequences from several budding yeasts revealed a core structure common to Saccharomyces and Kluyveromyces yeast species. We show that in this structure three conserved sequences interact to provide a binding site for Est2p positioned near the template. These results, combined with previous studies on telomerase RNAs from other budding yeasts, vertebrates, and ciliates, define a minimal universal core for telomerase RNAs.