Metabolite dependence of antibiotic susceptibility in a gut microbe.

Antibiotics save lives but can have unwanted effects on our gut microbes, thereby contributing to disease. A mechanistic understanding of how such microbes respond to antibiotics is hence critical. Recently in , Nilson et al.

Multicellular dynamics and wealth distribution in bacteria.

In a variety of infections, bacteria form multicellular communities which contribute to virulence and antibiotic tolerance. The molecular biology of such communities is actively studied, but our understanding of them remains incomplete. In this issue, Şimşek et al have developed and experimentally validated a dynamic model for community formation and revealed general insights into bacterial collective survival during antibiotic exposure.

self-organizes developmental rosettes.

Rosettes are self-organizing, circular multicellular communities that initiate developmental processes, like organogenesis and embryogenesis, in complex organisms. Their formation results from the active repositioning of adhered sister cells and is thought to distinguish multicellular organisms from unicellular ones. Though common in eukaryotes, this multicellular behavior has not been reported in bacteria.

Fluorescence-based protocol for revealing cellular arrangement in biofilms.

Standardized assays have greatly advanced the understanding of multicellular bacterial biofilms, but they lack cell-scale detail. Here, we present a fluorescence-based protocol that builds on past assays to reveal the cellular-scale arrangement within biofilms. We describe steps for growing biofilms on cover glass, followed by imaging and visualization of cellular arrangements in biofilms.

Resuscitation dynamics reveal persister partitioning after antibiotic treatment.

Bacteria can survive antibiotics by forming dormant, drug-tolerant persisters. Persisters can resuscitate from dormancy after treatment and prolong infections. Resuscitation is thought to occur stochastically, but its transient, single-cell nature makes it difficult to investigate.

Evidence of a possible multicellular life cycle in .

Biofilms are surface-attached multicellular microbial communities. Their genetics have been extensively studied, but the cell-scale morphogenetic events of their formation are largely unknown. Here, we recorded the entirety of morphogenesis in , and discovered a previously unknown multicellular self-assembly process.

Potentiating aminoglycoside antibiotics to reduce their toxic side effects.

The lack of new antibiotics necessitates the improvement of existing ones, many of which are limited by toxic side effects. Aminoglycosides, antibiotics with excellent activity and low bacterial resistance, are hampered by dose-dependent toxic effects in patients (nephrotoxicity, ototoxicity). High antibiotic concentrations are often required to treat dormant, non-dividing bacteria, though previous studies show that aminoglycosides can be activated against such bacteria by specific metabolites.

Increasing the speed of frequency-domain, homodyne thermoreflectance imaging.

Charge coupled device (CCD)-based thermoreflectance imaging using a "4-bucket" lock-in imaging algorithm is a well-established, powerful method for obtaining high spatial and thermal resolution two-dimensional thermal maps of optoelectronic, electronic, and micro-electro-mechanical systems devices. However, the technique is relatively slow, limiting broad commercial adoption. In this work, we examine the underlying limit on the image acquisition speed using the conventional "4-bucket" algorithm and show that the straightforward extension to an n-bucket technique by faster sampling does not address the underlying statistical bias in the data analysis and hence does not reduce the image acquisition time.

Antibiotics induce redox-related physiological alterations as part of their lethality.

Deeper understanding of antibiotic-induced physiological responses is critical to identifying means for enhancing our current antibiotic arsenal. Bactericidal antibiotics with diverse targets have been hypothesized to kill bacteria, in part by inducing production of damaging reactive species. This notion has been supported by many groups but has been challenged recently.

Salmonella typhimurium intercepts Escherichia coli signaling to enhance antibiotic tolerance.

Bacterial communication plays an important role in many population-based phenotypes and interspecies interactions, including those in host environments. These interspecies interactions may prove critical to some infectious diseases, and it follows that communication between pathogenic bacteria and commensal bacteria is a subject of growing interest. Recent studies have shown that Escherichia coli uses the signaling molecule indole to increase antibiotic tolerance throughout its population.

Body dysmorphia and plastic surgery.

Body dysmorphic disorder is a mental disorder characterized by a preoccupation with some aspect of one's appearance. In cosmetic surgery, this preoccupation can be overlooked by practitioners resulting in a discrepancy between expected and realistic outcome. Identifying the characteristics of this disorder may be crucial to the practitioner-patient relationship in the plastic surgery setting.

Wisdom of crowds for robust gene network inference.

Reconstructing gene regulatory networks from high-throughput data is a long-standing challenge. Through the Dialogue on Reverse Engineering Assessment and Methods (DREAM) project, we performed a comprehensive blind assessment of over 30 network inference methods on Escherichia coli, Staphylococcus aureus, Saccharomyces cerevisiae and in silico microarray data. We characterize the performance, data requirements and inherent biases of different inference approaches, and we provide guidelines for algorithm application and development.

Signaling-mediated bacterial persister formation.

Here we show that bacterial communication through indole signaling induces persistence, a phenomenon in which a subset of an isogenic bacterial population tolerates antibiotic treatment. We monitor indole-induced persister formation using microfluidics and identify the role of oxidative-stress and phage-shock pathways in this phenomenon. We propose a model in which indole signaling 'inoculates' a bacterial subpopulation against antibiotics by activating stress responses, leading to persister formation.

Heterogeneous bacterial persisters and engineering approaches to eliminate them.

Bacterial persistence is a state in which a subpopulation of cells (persisters) survives antibiotic treatment, and has been implicated in the tolerance of clinical infections and the recalcitrance of biofilms. There has been a renewed interest in the role of bacterial persisters in treatment failure in light of a wealth of recent findings. Here we review recent laboratory studies of bacterial persistence.

Metabolite-enabled eradication of bacterial persisters by aminoglycosides.

Bacterial persistence is a state in which a sub-population of dormant cells, or 'persisters', tolerates antibiotic treatment. Bacterial persisters have been implicated in biofilms and in chronic and recurrent infections. Despite this clinical relevance, there are currently no viable means for eradicating persisters.

Bacteria as control engineers.

Bacteria encounter fluctuations in both their external and internal environments, and to manage these conditions, they employ various control mechanisms. In this issue of Molecular Cell, Hart et al. (2011) investigate how E.