Correction: Enabling direct microcalorimetric measurement of metabolic activity and exothermic reactions onto microfluidic platforms via heat flux sensor integration.

[This corrects the article DOI: 10.1038/s41378-023-00525-z.].

Experimental In Vitro Microfluidic Calorimetric Chip Data towards the Early Detection of Infection on Implant Surfaces.

Heat flux measurement shows potential for the early detection of infectious growth. Our research is motivated by the possibility of using heat flux sensors for the early detection of infection on aortic vascular grafts by measuring the onset of bacterial growth. Applying heat flux measurement as an infectious marker on implant surfaces is yet to be experimentally explored.

Non-invasive monitoring of microbiota and host metabolism using secondary electrospray ionization-mass spectrometry.

The metabolic "handshake" between the microbiota and its mammalian host is a complex, dynamic process with major influences on health. Dissecting the interaction between microbial species and metabolites found in host tissues has been a challenge due to the requirement for invasive sampling. Here, we demonstrate that secondary electrospray ionization-mass spectrometry (SESI-MS) can be used to non-invasively monitor metabolic activity of the intestinal microbiome of a live, awake mouse.

Nanoscale clustering by O-antigen-Secretory Immunoglobulin-A binding limits outer membrane diffusion by encaging individual cells.

Secreted immunoglobulins, predominantly SIgA, influence the colonization and pathogenicity of mucosal bacteria. While part of this effect can be explained by SIgA-mediated bacterial aggregation, we have an incomplete picture of how SIgA binding influences cells independently of aggregation. Here we show that akin to microscale crosslinking of cells, SIgA targeting the Typhimurium O-antigen extensively crosslinks the O-antigens on the surface of individual bacterial cells at the nanoscale.

Enabling direct microcalorimetric measurement of metabolic activity and exothermic reactions onto microfluidic platforms via heat flux sensor integration.

All biological processes use or produce heat. Traditional microcalorimeters have been utilized to study the metabolic heat output of living organisms and heat production of exothermic chemical processes. Current advances in microfabrication have made possible the miniaturization of commercial microcalorimeters, resulting in a few studies on the metabolic activity of cells at the microscale in microfluidic chips.

Fitness advantage of capsular polysaccharide in the mouse gut depends on the resident microbiota.

Many microbiota-based therapeutics rely on our ability to introduce a microbe of choice into an already-colonized intestine. In this study, we used genetically barcoded () strains to quantify population bottlenecks experienced by a population during colonization of the mouse gut. As expected, this reveals an inverse relationship between microbiota complexity and the probability that an individual wildtype clone will colonize the gut.

Metabolic reconstitution of germ-free mice by a gnotobiotic microbiota varies over the circadian cycle.

The capacity of the intestinal microbiota to degrade otherwise indigestible diet components is known to greatly improve the recovery of energy from food. This has led to the hypothesis that increased digestive efficiency may underlie the contribution of the microbiota to obesity. OligoMM12-colonized gnotobiotic mice have a consistently higher fat mass than germ-free (GF) or fully colonized counterparts.

Smart investment of virus RNA testing resources to enhance Covid-19 mitigation.

A variety of mitigation strategies have been employed against the Covid-19 pandemic. Social distancing is still one of the main methods to reduce spread, but it entails a high toll on personal freedom and economic life. Alternative mitigation strategies that do not come with the same problems but are effective at preventing disease spread are therefore needed.

A rationally designed oral vaccine induces immunoglobulin A in the murine gut that directs the evolution of attenuated Salmonella variants.

The ability of gut bacterial pathogens to escape immunity by antigenic variation-particularly via changes to surface-exposed antigens-is a major barrier to immune clearance. However, not all variants are equally fit in all environments. It should therefore be possible to exploit such immune escape mechanisms to direct an evolutionary trade-off.

Dynamic modelling to identify mitigation strategies for the COVID-19 pandemic.

Relevant pandemic-spread scenario simulations can provide guiding principles for containment and mitigation policies. We devised a compartmental model to predict the effectiveness of different mitigation strategies with a main focus on mass testing. The model consists of a set of simple differential equations considering the population size, reported and unreported infections, reported and unreported recoveries, and the number of COVID-19-inflicted deaths.

Growing, evolving and sticking in a flowing environment: understanding IgA interactions with bacteria in the gut.

Immunology research in the last 50 years has made huge progress in understanding the mechanisms of anti-bacterial defense of deep, normally sterile, tissues such as blood, spleen and peripheral lymph nodes. In the intestine, with its dense commensal microbiota, it seems rare that this knowledge can be simply translated. Here we put forward the idea that perhaps it is not always the theory of immunology that is lacking to explain mucosal immunity, but rather that we have overlooked crucial parts of the mucosal immunological language required for its translation: namely intestinal and bacterial physiology.

Microbiota-derived peptide mimics drive lethal inflammatory cardiomyopathy.

Myocarditis can develop into inflammatory cardiomyopathy through chronic stimulation of myosin heavy chain 6-specific T helper (T)1 and T17 cells. However, mechanisms governing the cardiotoxicity programming of heart-specific T cells have remained elusive. Using a mouse model of spontaneous autoimmune myocarditis, we show that progression of myocarditis to lethal heart disease depends on cardiac myosin-specific T17 cells imprinted in the intestine by a commensal species peptide mimic.

Escherichia coli limits Salmonella Typhimurium infections after diet shifts and fat-mediated microbiota perturbation in mice.

The microbiota confers colonization resistance, which blocks Salmonella gut colonization. As diet affects microbiota composition, we studied whether food composition shifts enhance susceptibility to infection. Shifting mice to diets with reduced fibre or elevated fat content for 24 h boosted Salmonella Typhimurium or Escherichia coli gut colonization and plasmid transfer.

Bacterial growth, flow, and mixing shape human gut microbiota density and composition.

The human gut microbiota is highly dynamic, and host physiology and diet exert major influences on its composition. In our recent study, we integrated new quantitative measurements on bacterial growth physiology with a reanalysis of published data on human physiology to build a comprehensive modeling framework. This can generate predictions of how changes in different host factors influence microbiota composition.

Effect of water flow and chemical environment on microbiota growth and composition in the human colon.

The human gut harbors a dynamic microbial community whose composition bears great importance for the health of the host. Here, we investigate how colonic physiology impacts bacterial growth, which ultimately dictates microbiota composition. Combining measurements of bacterial physiology with analysis of published data on human physiology into a quantitative, comprehensive modeling framework, we show how water flow in the colon, in concert with other physiological factors, determine the abundances of the major bacterial phyla.

Effect of flow and peristaltic mixing on bacterial growth in a gut-like channel.

The ecology of microbes in the gut has been shown to play important roles in the health of the host. To better understand microbial growth and population dynamics in the proximal colon, the primary region of bacterial growth in the gut, we built and applied a fluidic channel that we call the "minigut." This is a channel with an array of membrane valves along its length, which allows mimicking active contractions of the colonic wall.

Genetic Manipulation of Glycogen Allocation Affects Replicative Lifespan in E. coli.

In bacteria, replicative aging manifests as a difference in growth or survival between the two cells emerging from division. One cell can be regarded as an aging mother with a decreased potential for future survival and division, the other as a rejuvenated daughter. Here, we aimed at investigating some of the processes involved in aging in the bacterium Escherichia coli, where the two types of cells can be distinguished by the age of their cell poles.

How type 1 fimbriae help Escherichia coli to evade extracellular antibiotics.

To survive antibiotics, bacteria use two different strategies: counteracting antibiotic effects by expression of resistance genes or evading their effects e.g. by persisting inside host cells.

Bistable expression of virulence genes in salmonella leads to the formation of an antibiotic-tolerant subpopulation.

Phenotypic heterogeneity can confer clonal groups of organisms with new functionality. A paradigmatic example is the bistable expression of virulence genes in Salmonella typhimurium, which leads to phenotypically virulent and phenotypically avirulent subpopulations. The two subpopulations have been shown to divide labor during S.

Antibiotic treatment selects for cooperative virulence of Salmonella typhimurium.

Antibiotics are powerful therapeutics but are not equally effective against all cells in bacterial populations. Bacteria that express an antibiotic-tolerant phenotype ("persisters") can evade treatment [1]. Persisters can cause relapses of the infection after the end of the therapy [2].

Antagonism between bacteriostatic and bactericidal antibiotics is prevalent.

Combination therapy is rarely used to counter the evolution of resistance in bacterial infections. Expansion of the use of combination therapy requires knowledge of how drugs interact at inhibitory concentrations. More than 50 years ago, it was noted that, if bactericidal drugs are most potent with actively dividing cells, then the inhibition of growth induced by a bacteriostatic drug should result in an overall reduction of efficacy when the drug is used in combination with a bactericidal drug.

Monitoring of dynamic microbiological processes using real-time flow cytometry.

We describe a straightforward approach to continuously monitor a variety of highly dynamic microbiological processes in millisecond resolution with flow cytometry, using standard bench-top instrumentation. Four main experimental examples are provided, namely: (1) green fluorescent protein expression by antibiotic-stressed Escherichia coli, (2) fluorescent labeling of heat-induced membrane damage in an autochthonous freshwater bacterial community, (3) the initial growth response of late stationary E. coli cells inoculated into fresh growth media, and (4) oxidative disinfection of a mixed culture of auto-fluorescent microorganisms.

Evolution of stress response in the face of unreliable environmental signals.

Most organisms live in ever-changing environments, and have to cope with a range of different conditions. Often, the set of biological traits that are needed to grow, reproduce, and survive varies between conditions. As a consequence, organisms have evolved sensory systems to detect environmental signals, and to modify the expression of biological traits in response.

The cost of virulence: retarded growth of Salmonella Typhimurium cells expressing type III secretion system 1.

Virulence factors generally enhance a pathogen's fitness and thereby foster transmission. However, most studies of pathogen fitness have been performed by averaging the phenotypes over large populations. Here, we have analyzed the fitness costs of virulence factor expression by Salmonella enterica subspecies I serovar Typhimurium in simple culture experiments.