A fraction of a genetically homogeneous microbial population may survive exposure to stress such as antibiotic treatment. Unlike resistant mutants, cells regrown from persistent bacteria remain sensitive the antibiotic. We investigated persistence single Escherichia coli with use microfluidic devices. Persistence was linked preexisting heterogeneity in bacterial populations because phenotypic switching occurred between normally growing and persister having reduced growth rates. Quantitative...

All About Noise How individual cells behave within a larger “average” population can be surprising. Wakamoto et al. (p. 91 ) developed method for investigating the consequences of phenotypic variability in single mycobacterial exposed to pro-drug, isoniazid. Isoniazid needs activated by bacterial catalase. In isoniazid–mycobacterium system, random fluctuations catalase activity were important cell survival. Because is essential, it cannot ablated; however, pulsed randomly mycobacteria. Thus,...

A key aspect of bacterial survival is the ability to evolve while migrating across spatially varying environmental challenges. Laboratory experiments, however, often study evolution in well-mixed systems. Here, we introduce an experimental device, microbial and growth arena (MEGA)–plate, which bacteria spread evolved on a large antibiotic landscape (120 × 60 centimeters) that allowed visual observation mutation selection front. While resistance increased consistently, multiple coexisting...

Antimicrobial treatments increasingly rely on multidrug combinations, in part because of the emergence and spread antibiotic resistance. The continued effectiveness combination depends crucially frequency with which resistance arises. Yet, it is unknown how this propensity for cross-resistance epistatic interactions-ranging from synergy to antagonism-between drugs. Here, we analyzed interactions between pairs drugs affect spontaneous medically important pathogen Staphylococcus aureus....

The rapid proliferation of antibiotic-resistant pathogens has spurred the use drug combinations to maintain clinical efficacy and combat evolution resistance. Drug pairs can interact synergistically or antagonistically, yielding inhibitory effects larger smaller than expected from drugs' individual potencies. Clinical strategies often favor synergistic interactions because they maximize rate at which infection is cleared an individual, but it unclear how such affect multi-drug We used a...

Bacteria in groups vary individually, and interact with other bacteria the environment to produce population-level patterns of gene expression. Investigating such behavior detail requires measuring controlling populations at single-cell level alongside precisely specified interactions environmental characteristics. Here we present an automated, programmable platform that combines image-based expression growth measurements on-line optogenetic control for hundreds individual Escherichia coli...

Abstract Antibiotic-sensitive and -resistant bacteria coexist in natural environments with low, if detectable, antibiotic concentrations. Except possibly around localized sources, where resistance can provide a strong advantage, bacterial fitness is dominated by stresses unaffected to the antibiotic. How do such mixed heterogeneous conditions influence selective advantage or disadvantage of resistance? Here we find that sub-inhibitory levels tetracyclines potentiate selection for against...

Bacteria regulate genes to survive antibiotic stress, but regulation can be far from perfect. When is not optimal, mutations that change gene expression contribute resistance. It systematically understood what extent natural or optimal for distinct antibiotics, and how changes in of specific quantitatively affect Here we discover a simple quantitative relation between fitness, expression, potency, which rationalizes our observation multitude even innate defense mechanisms have critically...

Antibiotics increase the frequency of resistant bacteria by providing them a competitive advantage over sensitive strains. Here, we develop versatile assay for differential chemical inhibition competing microbial strains, and use it to identify compounds that preferentially inhibit tetracycline-resistant relative bacteria, thus "inverting" selection resistance. Our distinguishes selecting directly against specific resistance mechanisms whose is based on their physiological interaction with...

All instances of the symbols t_ant_clear and t_syn_clear relating to Figures 4 S2 should instead read N_ant_double N_syn_double respectively. Similarly, all sigma_syn/sigma_ant S3 N_ant_double/N_syn_double.

Members of the genus Proteus are widely distributed in nature. They may also be present as saprophytes intestinal tract normal human beings. Only rarely they encountered primary causative agents diseases man. More frequently play role secondary invaders. Thus found association with infections urinary tract, perforative peritonitis, cholecystitis, ear and mastoid, conjunctivitis, puerperal fever, traumatic other anomalies. Although members have been isolated cultures material from patients...

Many antibiotics that are used in healthcare, farming, and aquaculture end up environments with different spatial structures might promote heterogeneity the emergence of antibiotic resistance. However, experimental evolution microbes at sub-inhibitory concentrations has been mainly carried out population level which does not allow capturing single-cell responses to antibiotics. Here, we investigate compare resistance ciprofloxacin

Understanding and characterising biochemical processes inside single cells requires experimental platforms that allow one to perturb observe the dynamics of such as well computational methods build parameterise models from collected data. Recent progress with optogenetics has made it possible expose each cell in an experiment individualised input automatically record cellular responses over days fine time resolution. However, infer parameters stochastic kinetic single-cell longitudinal data...

An alarming rise in antimicrobial resistance worldwide has spurred efforts into the search for alternatives to antibiotic treatments. The use of bacteriophages, bacterial viruses harmless humans, represents a promising approach with potential treat infections (phage therapy). Recent advances microscopy-based single-cell techniques have allowed researchers develop new quantitative methodologies assessing interactions between bacteria and phages, especially ability phages eradicate pathogen...

Abstract Many antibiotics that are used in healthcare, farming and aquaculture end up environments with different spatial structures might promote heterogeneity the emergence of antibiotic resistance. However, experimental evolution microbes at sub-inhibitory concentrations has been mainly carried out population level which does not allow capturing within bacterial populations. Here we investigate compare resistance to ciprofloxacin Escherichia coli well mixed structured using evolution,...

Attachment of adhesive molecules on cell culture surfaces to restrict adhesion defined areas and shapes has been vital for the progress in vitro research. In currently existing patterning methods, a combination pattern properties such as stability, precision, specificity, high-throughput outcome, spatiotemporal control is highly desirable but challenging achieve. Here, we introduce versatile covalent photoimmobilization technique, comprising light-dose-dependent step subsequent...