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. Previous article in issue. (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)

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)

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)

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 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)

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)

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)

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)

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)

While a number of valid molecular targets have been discovered for tumours over the past decade, finding an effective way of delivering therapeutic genes specifically to tumours has proved more problematic. A variety of viral and non‐viral delivery vehicles have been developed and applied in anti‐cancer gene therapies. However, these suffer from either inefficient and/or short‐lived gene transfer to target cells, instability in the bloodstream and inadequate tumour targeting. Recently, various types of non‐pathogenic obligate anaerobic and facultative anaerobic bacteria (...) have been shown to infiltrate and selectively replicate within solid tumours when delivered systemically. This has prompted the development of cancer gene therapy protocols that use such bacteria as gene delivery vehicles. Here, we review the evidence for the success of these in pre‐clinical models and clinical trials, as single modality treatments and in combination with conventional cancer therapies. BioEssays 28:84–94, 2006. © 2005 Wiley Periodicals, Inc. (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)

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)

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)

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)

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)

In Pieces of mind, Figdor examines how to interpret psychological predicates that scientists assign to entities that commonsensically do not have a mind such as neurons and plants. She claims that these predicates are used literally to refer to the same structures in humans and non‐human entities. I argue on the contrary that most uses of this kind are merely the extension of preexisting, possibly behaviorist senses of the relevant psychological predicates.

The discovery of fossil melanosomes has resulted in a wealth of research over the last 7 years, notably the reconstruction of colour in dinosaurs and fossil mammals. In spite of these discoveries some authors persist in arguing that the observed microbodies could represent preserved bacteria. They contend that bacteria fossilise easily and everywhere, which means that one can never be certain that a microbody is a melanosome without an extraordinary burden of evidence. However, this critique mischaracterises the morphological (...) and structural evidence for interpreting microbodies as fossil melanosomes, and hence the basis for using them in reconstructing prehistoric colours. The claims for bacterial omnipresence in the fossil record are themselves not supported, thus tipping the scales strongly towards melanosomes in the bacteria‐versus‐melanosome controversy. (shrink)

Insight into animal biology and development provided by classical genetic analysis of the model organism Drosophila melanogaster was an incentive to develop advanced genetic tools for this insect. But genetic systems for the over one million other known insect species are largely undeveloped. With increasing information about insect genomes resulting from next generation sequencing, RNA interference is now the method of choice for reverse genetics, although it is constrained by the means of delivery of interfering RNA. A recent advance to (...) ensure sustained delivery with minimal experimental intervention or trauma to the insect is to exploit commensal bacteria for symbiont‐mediated RNA interference. This technology not only offers an efficient means for RNA interference in insects in laboratory conditions, but also has potential for use in the control of human disease vectors, agricultural pests and pathogens of beneficial insects. (shrink)

Drug‐resistant bacterial infections constitute a major threat to global public health. Several key bacteria that are becoming increasingly resistant are among those that are ubiquitously carried by human beings and usually cause no symptoms (i.e. individuals are asymptomatic carriers) until and/or unless a precipitating event leads to symptomatic infection (and thus disease). Carriers of drug‐resistant bacteria can also transmit resistant pathogens to others, thus putting the latter at risk of resistant infections. Accumulating evidence suggests that such transmission occurs (...) not only in hospital settings but also in the general community, although considerably more data are needed to assess the extent of this problem. Asymptomatic carriage of drug‐resistant bacteria raises important ethical questions regarding the appropriate public health response, including the degree to which it would be justified to impose burdens on asymptomatic carriers (and others) in order to prevent transmission. In this paper, we (i) summarize current evidence regarding the carriage of key drug‐resistant bacteria, noting important knowledge gaps; and (ii) explore the particular implications of existing public health ethics frameworks for policy‐making regarding asymptomatic carriers. Inter alia, we argue that the relative burdens imposed by public health measures on healthy carriers (as opposed to sick individuals) warrant careful consideration and should be proportionate to the expected public health benefits in terms of risks averted. We conclude that more surveillance and research regarding community transmission will be needed in order to clarify relevant risks and design proportionate policies, although extensive community surveillance itself would also require careful ethical consideration. (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)

En este trabajo analizamos críticamente el enfoque mecanicista de explicación científica centrándonos principalmente en la forma en la que este da cuenta de los fenómenos biológicos. Nos proponemos complementar esta perspectiva con una concepción de nivel como intervalo de cuasi-descomponibilidad que nos permite fundamentar metafísicamente las propuestas mecanicistas clásicas en las propiedades sistémicas características de las entidades biológicas. A través del análisis de ejemplos concretos, demostraremos cómo nuestra propuesta permite superar algunas de las limitaciones de los enfoques predominantes de explicación (...) mecanística. (shrink)

Microalgae in the wild often form consortia with other species promoting their own health and resource foraging opportunities. The recent application of microalgae cultivation and deployment in commercial photobioreactors (PBR) so far has focussed on single species of algae, resulting in multi-species consortia being largely unexplored. Reviewing the current status of PBR ecological habitat, this article argues in favor of further investigation into algal communication with conspecifics and interspecifics, including other strains of microalgae and bacteria. These mutualistic species form (...) the ‘phycosphere’: the micro-environment surrounding microalgal cells, potentiating the production of certain metabolites through biochemical interaction with cohabitating microorganisms. A better understanding of the phycosphere could lead to novel PBR configurations, capable of incorporating algal-microbial consortia, potentially proving more effective than single-species algal systems. (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)

My description of the cognitive processes involved in the discovery, development, and acceptance of the bacterial theory of ulcers might have left the impression that science is all in the mind (Thagard, forthcoming-b). But only part of the story of the bacterial theory of ulcers is psychological. This paper discusses the important role of physical interaction with the world by means of instruments and experiments, and the equally important role of social interactions among the medical researchers who developed the theory. (...) The main questions I want to answer are the following: 1. What instruments contributed to the development and acceptance of the new theory? 2. What kinds of experiments contributed to the development and acceptance of the new theory? 3. How did theorizing and experimentation interact in the development of new experiments and hypotheses? 4. How did social processes such as collaboration, communication, and consensus contribute to the development and widespread acceptance of the bacterial theory of ulcers? I conclude with a sketch of science as a complex system of interacting psychological, physical, and social processes. (shrink)

The pathogenic, Gram‐negative bacteria, Neisseria gon‐orrhoeae, Neisseria meningitidis and Haemophilus influenzae, secrete immunoglobulin A1 proteases into their extracellular surroundings. An extraordinary feature in the secretory pathway of these putative virulence factors is a self‐directed outer membrane transport step allowing the proteins to be secreted autonomously, even from foreign Gram‐negative host cells like Escherichia coli. Here we summarize recent achievements in the understanding of IgA protease outer membrane translocation.

y interest in paleontology began in a childhood fascination with dinosaurs. I spent a substantial part of my youth reading the modest literature then available for children on the history of life. I well remember the invariant scheme used to divide the fossil record into a series of "ages" representing the progress that supposedly marked the march of evolution: the "Age of Invertebrates," followed by the Age of Fishes, Reptiles, Mammals and, finally, with all the parochiality of the engendered language (...) then current, the "Age of Man.". (shrink)

In order to explain several discrepancies between the gene-recombination phenomena in phages and in higher organisms, we assume that theT 2 phage, after entering the bacterium, divides in three parts corresponding to the three “chromosomes' whichHershey andRotman have traced in this phage. The three parts are supposed to be able to divide further by rupture or by the action of other “chromosome fragments”. Each fragment is supposed able to reproduce inside the bacterium as a more or less independent unit and (...) before lysis of the bacterium the various parts are assumed to reunite in complete sets of genes each forming a new phage.After discussing the experimental facts supporting these assumptions, we show that the assumptions are in perfect agreement with the theory of the symbiosis of genes, a theory which seems necessary in order to explain the ability of the “chromosome-fragments” to reunite into complete phages.Also the problems arising with respect to the sexual reproduction in bacteria is discussed under the point of view of the symbiosis theory. The assumption is made that the hereditary material is transduced from bacterium to bacterium by ultramicroscopic virus-like particles “genophores”. In several lysogenic bacteria the genophores are supposed still able to act as parasites instead of symbiontes towards some other sensitive bacteria. The experimental facts supporting this assumption are analyzed, and new experimental tests suggested. (shrink)

The ongoing controversy about the possibility of directed mutations in bacteria is examined for its methodological, and thereby philosophical, implications. The method of fluctuation analysis, widely used to investigate whether mutations are random or directed, is described and subjected to a conceptual critique which shows that it cannot decide whether some mutations are directed while most are random. In this context, recent experiments that exploit this possibility to suggest that directed mutations occur in bacteria are described. Interpretive and (...) experimental responses to such claims are briefly analyzed. Finally it is argued that mere statistical analysis, such as fluctuation analysis, cannot resolve this dispute. What will probably be required is an investigation of mechanisms of mutagenesis, an investigation that is intrinsically reductive. (shrink)