In eukaryotes, small amounts of nitrite confer cytoprotection against ischemia/reperfusion‐related tissue damage in vivo, possibly via reduction to nitric oxide (NO) and inhibition of mitochondrial function. Several hemeproteins are involved in this protective mechanism, starting with deoxyhemoglobin, which is capable of reducing nitrite. In facultative aerobic bacteria, such as Pseudomonas aeruginosa, nitrite is reduced to NO by specialized heme‐containing enzymes called cd1 nitrite reductases. The details of their catalytic mechanism are summarized below, together with a hypothesis on the (...) biological role of the unusual d1‐heme, which, in the reduced state, shows unique properties (very high affinity for nitrite and exceptionally fast dissociation of NO). Our results support the idea that the nitrite‐based reactions of contemporary eukaryotes are a vestige of earlier bacterial biochemical pathways. The evidence that nitrite reductase activities of enzymes with different cellular roles and biochemical features still exist today highlights the importance of nitrite in cellular homeostasis. (shrink)

A marked feature of eukaryotic programmed cell death is an early drop in mitochondrial transmembrane potential. This results from the opening of permeability transition pores, which are composed of adenine nucleotide translocators and mitochondrial porins. The latter share striking similarites with bacterial porins, (including down‐regulation of their pore size by purine nucleotides), suggesting a common origin. The porins of some invasive bacteria play a crucial role during their accommodation inside the host cell and this co‐existence resembles the endosymbiotic origin (...) of mitochondria. The above observations suggest that early in eukaryotic evolution, former invaders may have used porin‐type channels to enter their host and to induce its death when the levels of its cytoplasmic purine nucleotides were dropped. The appearance of adenosine nucleotide translocators in the primitive eukaryotes, which permitted usage of the oxidative metabolism of the invaders, provided the basis for the permeability transition phenomena, now linked to the apoptotic process. Bcl‐2‐type molecules, being able to modulate the permeability transition pores by interaction with adenosine nucleotide translocators, may have played an essential role in conferring a means of controlling apoptosis. (shrink)

Accumulating data suggest that the eukaryotic cell originated from a merger of two prokaryotes, an archaeal host and a bacterial endosymbiont. However, since prokaryotes are unable to perform phagocytosis, the means by which the endosymbiont entered its host is an enigma. We suggest that a predatory or parasitic interaction between prokaryotes provides a reasonable explanation for this conundrum. According to the model presented here, the host in this interaction was an anaerobic archaeon with a periplasm‐like space. The predator was a (...) small (facultative) aerobic α‐proteobacterium, which penetrated and replicated within the host periplasm, and later became the mitochondria. Plausible conditions under which this interaction took place and circumstances that may have led to the contemporary complex eukaryotic cell are discussed. (shrink)

Acute aerobic exercise has been shown to improve fine motor skills and alter activation of the motor cortex. The intensity of exercise may influence M1 activation, and further impact whole-body motor skill performance. The aims of the current study were to compare a whole-body motor skill via a piano task following moderate-intensity training and high-intensity interval training, and to determine if M1 activation is linked to any such changes in performance. Nine subjects, aged 18 ± 1 years completed a (...) control, MIT, and HIIT trial followed by administration of a piano performance task. M1 activation was evaluated by measuring oxyhemoglobin and hemoglobin difference changes during post-exercise piano performance using functional near-infrared spectroscopy. The results indicate that piano performance scores were higher after the MIT trial, but not HIIT trial, compared to the control trial. A negative relationship was detected between heart rate during HIIT and post-HIIT piano scores. M1 activation was significantly increased after the HIIT trial. M1 activation was also positively associated with piano performance when exercise trials and all trials were combined. We found that acute moderate-intensity exercise led to an improvement in complex motor skill performance while higher-intensity exercise increased M1 activation. These results demonstrate that moderate-intensity exercise can prime the nervous system for the acquisition of whole-body motor skills, suggesting that similar exercise protocols may be effective in improving the outcomes of other motor tasks performed during regular routines of daily life. In addition, it appears that improvements in motor task performance may be driven by M1 activation. Our findings provide new mechanistic insight into the complex relationship between exercise intensity, M1 activation, and whole-body motor skill performance. (shrink)

Forty years’ experience as a bacterial geneticist has taught me that bacteria possess many cognitive, computational and evolutionary capabilities unimaginable in the first six decades of the twentieth century. Analysis of cellular processes such as metabolism, regulation of protein synthesis, and DNA repair established that bacteria continually monitor their external and internal environments and compute functional outputs based on information provided by their sensory apparatus. Studies of genetic recombination, lysogeny, antibiotic resistance and my own work on transposable elements (...) revealed multiple widespread bacterial systems for mobilizing and engineering DNA molecules. Examination of colony development and organization led me to appreciate how extensive multicellular collaboration is among the majority of bacterial species. Contemporary research in many laboratories on cell–cell signaling, symbiosis and pathogenesis show that bacteria utilise sophisticated mechanisms for intercellular communication and even have the ability to commandeer the basic cell biology of ‘higher’ plants and animals to meet their own needs. This remarkable series of observations requires us to revise basic ideas about biological information processing and recognise that even the smallest cells are sentient beings. (shrink)

In this paper, I discuss the recent discovery of alleged arsenic bacteria in Mono Lake, California, and the ensuing debate in the scientific community about the validity and significance of these results. By situating this case in the broader context of projects that search for anomalous life forms, I examine the methodology and upshots of challenging biochemical constraints on living things. I distinguish between a narrower and a broader sense in which we might challenge or change our knowledge of (...) life as the result of such a project, and discuss two different kinds of projects that differ in their potential to overhaul our knowledge of life. I argue that the arsenic bacteria case, while potentially illuminating, is the kind of constraint-challenging project that could not—in spite of what was said when it was presented to the public—change our knowledge of life in the deeper sense. (shrink)

With roots in Greek drama, mimesis has recently undergone expansion into an unexpected domain: microbial resistance to viruses. Research revealed that bacteria copy portions of the DNA of attacking viruses and incorporate them into their own DNA. When a virus attacks again, the bacteria generate matching RNA sequences that, together with the Cas9 protein, enable them to recognize the virus and cut its DNA. This process satisfies the requisites for mimesis, thus justifying the name microbiomimesis. It exemplifies nonconscious (...) cognition, a capacity that all lifeforms possess to process and interpret information in contexts that connect it with meaning. In 2012 Jennifer Doudna and Emmanuelle Carpentier coauthored a paper showing that the bacterial defense of RNA/cas9 can be programmed to work as a gene editing tool. So was born CRISPR-Cas9, a technology now routinely used to edit genes by detecting their precise location and modifying them. Never has mimesis been so controversial and laden with implications for the futures of human and nonhuman lifeforms on the planet; what lessons can its traditions offer? (shrink)

Cybernetic Bacteria is an ongoing transdisciplinary investigation that brings together art, philosophy, microbiology and digital technology to examine the relationship of the emerging science of bacterial communication to our own digital communications networks, looking in particular at ‘packet data’ and bacterial quorum sensing. The project seeks to compare philosophical notions of the sublime with a kind of bacterial sublime, demonstrating the greater complexity of the interactions taking place at a microscopic level, when compared to human communication technologies such as (...) the World Wide Web (with particular focus on scale-free networks). The first artwork in the series employed a clear plastic tube of liquid agar jelly planted into earth to allow the soil bacteria beneath to grow upwards and become visible. A total of 100 µL of Homoserine Lactone, a hormone used by bacteria for quorum sensing (a form of bacterial communication), was then added by the artist as part of a performance lecture, with her in effect saying: ‘I’m here’ to the bacteria below. The microbes that have been communicated to then pass the signal on to their neighbours and so on. In theory this enables the signal to travel around the planet. However, the main issue with this work is one of Hermeneutics; the bacteria, which receive the communication, will not identify the artist as human – simply as another (albeit very large) bacterium. The project has subsequently evolved into a multiple screen digital artwork showing network traffic taking place in real time (web traffic, RFID and Bluetooth), a film of bacterial communication in progress (using two strains of genetically modified bacteria) and an interactive conceptualisation of the data from both sources generated using artificial life. The project continues. (shrink)

The ability to initiate DNA replication is a critical step in the proliferation of all organisms. In bacteria, this process is mediated by an ATP‐dependent replication initiator protein, DnaA, which recognizes and melts replication origin (oriC) elements. Despite decades of biochemical and structural work, a mechanistic understanding of how DnaA recognizes and unwinds oriC has remained enigmatic. A recent study by Pelliciari et al. provides important new structural insights into how DnaA from Bacillus subtilis recognizes and processes its cognate (...) oriC, showing how DnaA uses sequence features encoded in the origin to engage melted DNA. Comparison of the DnaA‐oriC structure with archaeal/eukaryl replication origin complexes based on Orc‐family proteins reveals a high degree of similarity in origin engagement by initiators from di domains of life, despite fundamental differences in origin melting mechanisms. These findings provide valuable insights into bacterial replication initiation and highlight the intriguing evolutionary history of this fundamental biological process. (shrink)

Philosophical discussions of species have focused on multicellular, sexual animals and have often neglected to consider unicellular organisms like bacteria. This article begins to fill this gap by considering what species concepts, if any, apply neatly to the bacterial world. First, I argue that the biological species concept cannot be applied to bacteria because of the variable rates of genetic transfer between populations, depending in part on which gene type is prioritized. Second, I present a critique of phylogenetic (...) bacterial species, arguing that phylogenetic bacterial classification requires a questionable metaphysical commitment to the existence of essential genes. I conclude by considering how microbiologists have dealt with these biological complexities by using more pragmatic and not exclusively evolutionary accounts of species. I argue that this pragmatism is not borne of laziness but rather of the substantial conceptual problems in classifying bacteria based on any evolutionary standard. (shrink)

The present study aimed to investigate the effects of acute aerobic exercise on underlying neuronal activities associated with task-switching processes including both mixing and switch costs. A total of 29 healthy young adults (21.4 ±1.2 years) participated in this study. The experiment consisted of an exercise and a rest condition. In the exercise condition, participants completed 30 minutes of walking and/or jogging on a motor driven treadmill sufficient to achieve an intensity of 70% of maximum heartrate (HRmax). In the (...) rest condition, participants rested quietly for 30 minutes. Both conditions were conducted on different days, and the order was counterbalanced across participants. Participants performed the task-switching paradigm (switching between two different tasks), after both exercise and rest conditions respectively. The P3 amplitude was smaller in the non-switch trial than the single trial only in the rest condition, but not in the exercise condition. In other words, more attentional resources were allocated to the non-switch trial requiring greater amounts of working memory following the exercise condition. Mixing and switch effects on the P3 component were influenced by acute aerobic exercise. This result suggests that acute aerobic exercise may serve to facilitate the flexibility of task-set reconfiguration and maintaining the task set in working memory. Furthermore, during the switch trials, the P3 latency was shorter in the exercise condition than in the rest condition. This result is consistent with the findings of previous studies, indicating that cognitive processing speed is increased only during task conditions requiring greater amounts of executive control. Our study clearly indicates that acute aerobic exercise may facilitate cognitive flexibility as well as other executive functions (i.e., inhibitory control and working memory). (shrink)

The purpose of this study was to observe whether aerobic exercise is able to alleviate the impairment of cognitive control ability in college students by sleep deprivation through cognitive control and blood-based markers. Taking 30 healthy college students as participants, using a random cross-over design within groups, respectively perform one night of sleep deprivation and one night of normal sleep. The exercise intervention modality was to complete a 30-min session of moderate-intensity aerobic exercise on a power bicycle. Change (...) in cognitive control was assessed using the Go/NoGo task paradigm; 5-ht and blood glucose contentwere determined by enzyme-linked immuno sorbent assay and glucose oxidase electrode Measurement, respectively. The results showed that sleep deprivation could significantly reduce the response inhibition ability and response execution ability, and significantly reduce the blood 5-ht content. Thirty minutes of moderate intensity aerobic exercise intervention significantly increased response inhibition ability and response execution ability, significantly increased blood 5-ht content, and did not change serum glucose levels. Conclusion: An acute aerobic exercise can alleviate the cognitive control impairment caused by sleep deprivation, and 5-ht may be one of the possible mechanisms by which aerobic exercise alleviates the cognitive control impairment caused by sleep deprivation. (shrink)

Among the theses promulgated by the Frankfort School theorists during the forties and fifties was the decline of the individual under contemporary capitalism. The chief agent of this decline was identified as the culture industry, which served the reigning system by integrating people into its particular regime of production, reproduction, and consumption. By dominating minds, homogenizing behaviors, and normalizing tastes, this industry prepared people for capitalist toil. In so doing, it also obstructed the flowering of individuality. Individuality, if it were (...) possible any longer, could henceforth be found only among the “captains” of capitalism in charge of the system. In fact, however, these captains were equally captive. The future of the individual thus seemed sealed. (shrink)

While largely studied because of their harmful effects on human health, there is growing appreciation that bacteria are important partners for invertebrates and vertebrates, including man. Epithelia in metazoans do not only select their microbiota; a coevolved consortium of microbes enables both invertebrates and vertebrates to expand the range of diet supply, to shape the complex immune system and to control pathogenic bacteria. Microbes in zebrafish and mice regulate gut epithelial homeostasis. In a squid, microbes control the development (...) of the symbiotic light organ. These discoveries point to a key role for bacteria in any metazoan existence, and imply that beneficial bacteria‐host interactions should be considered an integral part of development and evolution. (shrink)

Two tenets are of significant concern to today’s philosophers of science: one continues to be that age-old idea of Scientific Realism, the other is a more contemporary assertion of the Metaphysical Unity to science. Although the motivations for or against them are very different, there seems to be a payoff with the degree to which anyone has so-far been able to accept one given their acceptance of the other. Or at least, that is what a survey of recent debate would (...) seem to suggest. Why is this? I’ll hazard a guess after laying out what exactly the tenets claim and how philosophers have tried to orient themselves between them. (shrink)

Upon starvation and growth arrest, Escherichia coli cells gradually lose their ability to reproduce. These apparently sterile/nonculturable cells initially remain intact and metabolically active and the underlying molecular mechanism behind this sterility is something of an enigma in bacteriology. Three different models have been proposed to explain this phenomenon. The first theory suggests that starving cells become nonculturable due to cellular deterioration, are moribund, and show some of the same signs of senescence as aging organisms. The two other theories suggest (...) that genetically programmed pathways, rather than stochastic deterioration, trigger nonculturability. One “program” theory suggests that nonculturability is the culmination of an adaptive pathway generating dormant survival forms, similar to spore formation in differentiating bacteria. The other “program” theory states that starved cells lose viability due to activation of genetic modules mediating programmed cell death. The different models will be reviewed and evaluated in light of recent data on the physiology and molecular biology of growth‐arrested E. coli cells. BioEssays 25:204–211, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

Bacteria have a significant impact on human production and life, endangering human life and health, so rapid detection of infectious agents is essential to improve human health. Aptamers, which are pieces of oligonucleotides (DNA or RNA) have been applied to biosensors for bacteria detection due to their high affinity, selectivity, robust chemical stability, and their compatibility with various signal amplification and signal transduction mechanisms. In this review, we summarize the different bacterial aptamers selected in recent years using SELEX (...) technology and discuss the differences in optical and electrochemical bacterial aptamer sensors. In addition the technological developments and innovations in bacterial aptamer sensor technology are introduced. Combining new materials and methods, the efficiency and stability of the sensors have also been improved. This review summarizes the progress of current bacterial aptamer sensors based on their practical application status and provides an outlook on their future development. (shrink)

Teachers face significant stressors in relation to their work, placing them at increased risk for burnout and attrition. The COVID-19 pandemic has brought about additional challenges, resulting in an even greater burden. Thus, strategies for reducing stress that can be delivered virtually are likely to benefit this population. Mental and Physical (MAP) Training combines meditation with aerobic exercise and has resulted in positive mental and physical health outcomes in both clinical and subclinical populations. The aim of this pilot study (...) was to evaluate the feasibility and potential effectiveness of virtual MAP Training on reducing stress and improving mood and well-being in teachers. Participants (n= 104) were from recruited online from kindergarten to grade twelve (K-12) schools in the Northeastern region of the United States and randomly assigned to a 6-week program of virtual MAP Training (n= 58) or no training (n= 13). Primary outcomes included pre-intervention and post-intervention ratings on self-report measures of social and emotional health. Changes in cognitive functioning and physical health were also examined in secondary analyses. By intervention end, participants in the MAP Training group reported less anxiety and work-related stress compared to those who received no training (ds = −0.75 to −0.78). Additionally, MAP Training participants reported improvements in depressive symptoms, rumination, work-related quality of life, perceived stress, and self-compassion (ds = 0.38 to −0.82), whereas no changes were observed in the no training group. Participants also reported increased subjective ratings of executive functioning, working memory, cognitive flexibility, and fewer sleep disturbances (ds = −0.41 to −0.74). Together, these results suggest that the combination of meditation and aerobic exercise is an effective virtual intervention for improving mental health and well-being among K-12 teachers and may enhance resilience to stressful life events such as occurred during the coronavirus pandemic. (shrink)

Humans are driving the planet toward catastrophe, and yet humans are the only species capable of taking positive actions on a global scale to prevent collapse. For N. Katherine Hayles, human hubris and the anthropocentrism that underlies it is one of the main drivers of our current planetary crises. So, if we are to take action to save the planet, we urgently need to re-think basic assumptions about agency, decision-making, control, and our relations to nonhuman and artificial cognizers. In (...) class='Hi'>Bacteria to AI, Hayles develops an integrated cognitive framework (ICF) that includes humans, nonhuman lifeforms, and some computational media, including artificial intelligence. Bacteria to AI analyzes how the first-order emergences of physical phenomena, multicellularity, and technics are now interacting together to create second-order emergences that greatly accelerate technical developments. The book explores these entanglements through case studies ranging from gene editing to autopoiesis and Gaia theory, bacteria and xenobots to artificial intelligence. Spanning evolutionary biology, artificial intelligence, and contemporary literature, Bacteria to AI recognizes the risks of contemporary technologies but insists a positive way forward, with ICF at its core, is possible for us and for the more than human world. (shrink)

The timeline of the Anthropocene – a geological epoch that Paul Crutzen and Eugene Stoermer say began in the late 18th century with the invention of the steam engine – seems like a brief and inconsequential blip, against the time scales embodied by the microbial communities. Wolbachia bacteria predate Anthropos by some 150 million years, and will likely outlast us. Wolbachia bacteria are worthy of their own geological epoch because they offer a fresh vantage point on one of (...) the most pressing ethical questions of our time: ‘How should we love in a time of extinction?’ Narratives about the Wolbachiacene have the potential to disrupt the overwhelming stories of tragedy orbiting around Anthropos, with disquieting and generative accounts of interspecies romance. Wolbachia often perform queer tricks inside their invertebrate hosts. In some host species these bacteria induce parthenogenesis – completely eliminating males from the population. Wolbachia can also transform genetic males into reproductively viable females. (shrink)

The sociobiology of bacteria, largely unappreciated and ignored by the microbiology research community two decades ago is now a major research area, catalyzed to a significant degree by studies of communication and cooperative behavior among the myxobacteria and in quorum sensing (QS) and biofilm formation by pseudomonads and other microbes. Recently, the topic of multicellular cooperative behaviors among bacteria has been increasingly considered in the context of evolutionary biology. Here we discuss the significance of two recent studies1,2 of (...) the phenomenon of “cheating” mutants and their exploitation of cooperating microbial populations of Pseudomonas aeruginosa. BioEssays 30:296–298, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

The objective of this study was to correlate the presence of arsenic in roots and stems of Brachiaria humidicola cv. humidicola (Rendle) Schweick grown in cattle areas of the San Jorge subregion and the population density of endophytic bacteria in roots and foliage with the presence of this metal. Samples of soil, roots and stems of B. humicola grass were collected and characterized for arsenic concentration in roots and foliage and the presence of endophytic bacteria (CFU/g tissue). The (...) results show the presence of arsenic concentrations in roots and stems above the values established at national and international level. Likewise, the presence of endophytic bacteria was found in the roots and foliage of B. humidicola, which may be contributing to the remediation and reduction of arsenic concentration from the roots to the foliage. This is the first study correlating the presence of arsenic and endophytic bacteria on cattle farms with B. humicola and the possible role of these bacteria in contributing to bioremediation of this metal in the soil and within the tissues of the pasture species. (shrink)

In 1983, Dr. J. Robin Warren and Dr. Barry Marshall reported finding a new kind of bacteria in the stomachs of people with gastritis. Warren and Marshall were soon led to the hypothesis that peptic ulcers are generally caused, not by excess acidity or stress, but by a bacterial infection. Initially, this hypothesis was viewed as preposterous, and it is still somewhat controversial. In 1994, however, a U. S. National Institutes of Health Consensus Development Panel concluded that infection appears (...) to play an important contributory role in the pathogenesis of peptic ulcers, and recommended that antibiotics be used in their treatment. Peptic ulcers are common, affecting up to 10% of the population, and evidence has mounted that many ulcers can be cured by eradicating the bacteria responsible for them. (shrink)

Horizontal gene transfer advances bacterial evolution. To benefit from horizontally acquired genes, enteric bacteria must overcome silencing caused when the widespread heat‐stable nucleoid structuring (H‐NS) protein binds to AT‐rich horizontally acquired genes. This ability had previously been ascribed to both anti‐silencing proteins outcompeting H‐NS for binding to AT‐rich DNA and RNA polymerase initiating transcription from alternative promoters. However, we now know that pathogenic Salmonella enterica serovar Typhimurium and commensal Escherichia coli break down H‐NS when this silencer is not bound (...) to DNA. Curiously, both species use the same protease – Lon – to destroy H‐NS in distinct environments. Anti‐silencing proteins promote the expression of horizontally acquired genes without binding to them by displacing H‐NS from AT‐rich DNA, thus leaving H‐NS susceptible to proteolysis and decreasing H‐NS amounts overall. Conserved amino acid sequences in the Lon protease and H‐NS cleavage site suggest that diverse bacteria degrade H‐NS to exploit horizontally acquired genes. (shrink)

Many bacteria that cause disease have the capacity to enter into and live within eukaryotic cells such as epithelial cells and macrophages. The mechanisms used by these organisms to achieve and maintain this intracellular lifestyle vary considerably, but most mechanisms involve subversion and exploitation of host cell functions. Entry into non‐phagocytic cells involves triggering host signal transduction mechanisms to induce rearrangement of the host cytoskeleton, thereby facilitating bacterial uptake. Once inside the host cell, intracellular pathogens either remain within membrane (...) bound inclusions or escape to the cytoplasm. Those living in the cytoplasm can further pirate the host actin system, using actin as a mechanism to facilitate movement within and between host cells. Organisms remaining within the vacuole have specialized mechanisms for intracellular survival and growth which involve additional communication with the host cell. Some of the processes involved in the various steps of facultative intracellular parasitism are discussed in the context of subverting the host cell cytoskeleton and signal transduction pathways for bacterial benefit. (shrink)

Whenever the state of a biological system is not determined solely by present conditions but depends on its past history, we can say that the system has memory. Bacteria and bacteriophage use a variety of memory mechanisms, some of which seem to convey adaptive value. A genetic type of heritable memory is the programmed inversion of specific DNA sequences, which causes switching between alternative patterns of gene expression. Heritable memory can also be based on epigenetic circuits, in which a (...) system with two possible steady states is locked in one or the other state by a positive feedback loop. Epigenetic states have been observed in a variety of cellular processes, and are maintained by diverse mechanisms. Some of these involve alternative DNA methylation patterns that are stably transmitted to daughter molecules and can affect DNA–protein interactions (e.g., gene transcription). Other mechanisms exploit autocatalytic loops whereby proteins establish the proper conditions for their continued synthesis. Template polymers other than nucleic acids (e.g., components of the cell wall) may also propagate epigenetic states. Non‐heritable memory is exemplified by parasitic organisms that bear a signature of their previous host, such as host‐controlled modification of phage DNA or porin hitchhiking in predatory bacteria. The heterogeneous nature of the examples known may be indicative of widespread occurrence of memory mechanisms in bacteria and phage. However, the actual extent, variety and potential selective value of prokaryotic memory devices remain open questions, still to be addressed experimentally. BioEssays 24:512–518, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

CRISPR (clustered regularly interspaced short palindromic repeats) activation (CRISPRa) in bacteria is an attractive method for programmable gene activation. Recently, a eukaryote‐like, σ54‐dependent CRISPRa system has been reported. It exhibits high dynamic ranges and permits flexible target site selection. Here, an overview of the existing strategies of CRISPRa in bacteria is presented, and the characteristics and design principles of the CRISPRa system are introduced. Possible scenarios for applying the eukaryote‐like CRISPRa system is discussed with corresponding suggestions for performance (...) optimization and future functional expansion. The authors envision the new eukaryote‐like CRISPRa system enabling novel designs in multiplexed gene regulation and promoting research in the σ54‐dependent gene regulatory networks among a variety of biotechnology relevant or disease‐associated bacterial species. (shrink)

The human immune system can directly lyse invading micro‐organisms and aberrant host cells by generating pores in the cell envelope, called membrane attack complexes (MACs). Recent studies using single‐particle cryoelectron microscopy have revealed that the MAC is an asymmetric, flexible pore and have provided a structural basis on how the MAC ruptures single lipid membranes. Despite these insights, it remains unclear how the MAC ruptures the composite cell envelope of Gram‐negative bacteria. Recent functional studies on Gram‐negative bacteria elucidate (...) that local assembly of MAC pores by surface‐bound C5 convertase enzymes is essential to stably insert these pores into the bacterial outer membrane (OM). These convertase‐generated MAC pores can subsequently efficiently damage the bacterial inner membrane (IM), which is essential for bacterial killing. This review summarizes these recent insights of MAC assembly and discusses how MAC pores kill Gram‐negative bacteria. Furthermore, this review elaborates on how MAC‐dependent OM damage could lead to IM destabilization, which is currently not well understood. A better understanding on how MAC pores kill bacteria could facilitate the future development of novel strategies to treat infections with Gram‐negative bacteria. (shrink)

Effectiveness is a key criterion in assessing the justification of antibiotic resistance interventions. Depending on an intervention’s effectiveness, burdens and costs will be more or less justified, which is especially important for large scale population-level interventions with high running costs and pronounced risks to individuals in terms of wellbeing, integrity and autonomy. In this paper, we assess the case of routine hospital screening for multi-drug-resistant Gram-negative bacteria (MDRGN) from this perspective. Utilizing a comparison to screening programs for Methicillin-Resistant Staphylococcus (...) aureus (MRSA) we argue that current screening programmes for MDRGN in low endemic settings should be reconsidered, as its effectiveness is in doubt, while general downsides to screening programs remain. To accomplish justifiable antibiotic stewardship, MDRGN screening should not be viewed as a separate measure, but rather as part of a comprehensive approach. The program should be redesigned to focus on those at risk of developing symptomatic infections with MDRGN rather than merely detecting those colonised. (shrink)