Simultaneous spatiotemporal transcriptomics and microscopy of Bacillus subtilis swarm development reveal cooperation across generations.

Development of microbial communities is a complex multiscale phenomenon with wide-ranging biomedical and ecological implications. How biological and physical processes determine emergent spatial structures in microbial communities remains poorly understood due to a lack of simultaneous measurements of gene expression and cellular behaviour in space and time. Here we combined live-cell microscopy with a robotic arm for spatiotemporal sampling, which enabled us to simultaneously acquire phenotypic imaging data and spatiotemporal transcriptomes during Bacillus subtilis swarm development. Quantitative characterization of the spatiotemporal gene expression patterns revealed correlations with cellular and collective properties, and phenotypic subpopulations. By integrating these data with spatiotemporal metabolome measurements, we discovered a spatiotemporal cross-feeding mechanism fuelling swarm development: during their migration, earlier generations deposit metabolites which are consumed by later generations that swarm across the same location. These results highlight the importance of spatiotemporal effects during the emergence of phenotypic subpopulations and their interactions in bacterial communities.

A genetic switch controls Pseudomonas aeruginosa surface colonization.

Efficient colonization of mucosal surfaces is essential for opportunistic pathogens like Pseudomonas aeruginosa, but how bacteria collectively and individually adapt to optimize adherence, virulence and dispersal is largely unclear. Here we identified a stochastic genetic switch, hecR-hecE, which is expressed bimodally and generates functionally distinct bacterial subpopulations to balance P. aeruginosa growth and dispersal on surfaces. HecE inhibits the phosphodiesterase BifA and stimulates the diguanylate cyclase WspR to increase c-di-GMP second messenger levels and promote surface colonization in a subpopulation of cells; low-level HecE-expressing cells disperse. The fraction of HecE+ cells is tuned by different stress factors and determines the balance between biofilm formation and long-range cell dispersal of surface-grown communities. We also demonstrate that the HecE pathway represents a druggable target to effectively counter P. aeruginosa surface colonization. Exposing such binary states opens up new ways to control mucosal infections by a major human pathogen.

Ameliorating the antimicrobial resistance crisis: phage therapy.

Propelled by the overuse and inappropriate use of antibiotics, antimicrobial resistance is now widespread in the environment, leaving us with limited drugs for treating a large number of resistant pathogens. The use of bacteriophages that kill bacteria has come up as a viable alternative to circumvent the antimicrobial resistance crisis, and phage therapy-based approaches are fast advancing in recent times. In this minireview, we try to describe the advantages associated with phage therapy and update the latest developments in the field including the clinical trials that are underway. Particularly, we highlight the synergistic bactericidal effect of phages in the presence of sub-lethal dose of antibiotics and the potency of lytic phages, and their hydrolytic enzymes in expunging pathogens from drug-tolerant biofilms and animal farm produce. We also discuss how major challenges, including human immune response to phage components, development of bacterial resistance and elimination of intracellular pathogens, presented as potential setbacks to the implementation of phage therapy is being removed using engineered phages and novel formulations. © 2019 IUBMB Life, 2019.