The new bacteriology

The field of Microbiology, in particular that of Bacteriology, has changed dramatically over the last 20 years, due to new technologies and new approaches that have benefited all fields of biology. The papers in this volume arise from a 2-day meeting entitled ‘The New Bacteriology’ held on 28 and 29 January 2016 at the Royal Society in London in partnership with the French Academy of Sciences and the German Leopoldina. It aimed to highlight new concepts and approaches that have led to a bona fide renaissance in the discipline of Bacteriology.

The meeting was divided into four sessions, each with four lectures, which covered areas that are currently studied intensively by bacteriologists. There was a session on bacterial evolution and diversity, one session covering the social life of bacteria, another highlighting advances in bacterial cell biology and a final session on infection biology (in the broadest sense) and drug resistance.

The first session opened with an in-depth consideration by Knoll [1] (Harvard University and MIT, USA) on life 2 billion years ago, discussing the presence of bacteria in stromatolites and other sedimentary rocks. The first billion years of biological and environmental evolution featured bacteria and archaea living in oceans with much iron, but little oxygen. Over the next billions of years, as oceans came to have less iron, but more oxygen, aerobic metabolism expanded the metabolic diversity of prokaryotic microorganisms, while hybrid eukaryotic cells with new and different organizations emerged. The second talk by Errington [2] (Newcastle University, UK) concerned a particular status of bacteria, the L-forms—which are bacteria without a cell wall. These bacteria are completely resistant to most antibiotics that act specifically on cell wall synthesis, such as penicillins and cephalosporins, which is consistent with reports of L-forms associated with various chronic diseases. Important outstanding issues concern their appearance, mode of division and physiological significance. Julian Parkhill (Wellcome Trust Sanger Institute, UK) discussed the application of genome-wide sequence analysis using Salmonella and Mycobacterium abscessus as examples. Using a large number of bacterial strains, phylogenetic lineages can be established that in turn provide hypotheses regarding the transmission, evolution and basis of pathogenic clones. The last talk of the session was by Charpentier [3] (Max Planck Institute for Infection Biology, Germany) who delivered an historical perspective on the various CRISPR systems, their discovery, nomenclature, role in phage resistance, plasmid transfer and on their possible applications—including ethical problems arising from the genome editing technologies.

In the second session, Hengge [4] (Humboldt Universitat Zu Berlin, Germany) gave an overview on biofilm formation and the role of cyclic diGMP (c-di-GMP). This molecule appears to be critical in biofilm formation and in cell cycle progression, development and virulence. Its synthesis and degradation are tightly controlled by enzymes that are numerous in bacterial cells and which mediate localized signalling. Effectors of c-di-GMP include riboswitches and proteins including the so-called trigger phospodiesterases which appear as a novel class of c-di-GMP sensing effector proteins. Basler [5] (Biozentrum, University of Basel, Switzerland) reviewed our current understanding of type VI secretion systems and illustrated how the systems share a number of properties with phage contractile tails, as demonstrated by the use of high-speed imaging of sheath assembly, contraction and disassembly. He also presented videos illustrating, by single-cell analysis, how the type VI systems are used by bacteria to attack and retaliate against attack from other bacteria in multibacterial communities. Sansonetti [6] (Institut Pasteur, France) illustrated how the microbiota participates in intestinal life and immune development. He first described a genetic screen to identify genes of Lactobacillus casei involved in commensalism. He then described how his group has been able to cultivate mouse ileal segmented filamentous bacteria, which are critical for the development of a variety of immune responses. He demonstrated that crypts are populated by Acinetobacter and Delftia/Comamonas (aerobic non-fermentative genera) and also by Bacteroides fragilis, forming what is called the crypt-specific core microbiota (CSCM). Sansonetti also described the use of ‘miniguts’ or organoids for the study of the CSCM and concluded by emphasizing the importance of studying not only murine but also human crypts. Chassaing [7] (Georgia State University, USA) gave a broad presentation on the microbiota and its role in direct protection and enhancing host protection from pathogens. While the microbiota provides protection against a number of diseases, disturbance of the microbiota/host interaction can induce numerous chronic inflammatory diseases including inflammatory bowel disease and a group of obesity-associated diseases collectively referred to as metobolic syndrome. The mucus layer is an important protective barrier that keeps the microbiota at a distance from the epithelium. Chassaing described how detergent-like food emulsifiers can interfere with intestinal homeostasis.

The third session began with a presentation by Venki Ramakhrishnan (Royal Society President, MRC Laboratory for Molecular Biology, Cambridge, UK) on ribosome-dependent activation of stringent control in response to bacterial stress. He provided an elegant structural explanation for how a key protein—RelA—recognizes stalled ribosomes and he proposed that RelA might be a good target for novel antibacterial agents. Armitage [8] (Oxford University, UK) described how her group uses bacteria transformed with proteins labelled with fluorescent dyes to investigate, at the single cell level, and in real time, signal transduction between CheY molecules diffusing inside cells and travelling between sensory clusters and flagella motors. Imaging resolution now approaches the single molecule level, providing a beautiful demonstration of the extraordinary precision that modern light microscopy can now deliver. Gründling [9] (Imperial College London, UK) gave an overview on the series of novel nucleotide-derived signalling molecules at work in the bacterial cell. She also described the tools established to analyse their concentration, including FRET sensors, and the approaches taken for the identification of the nucleotide receptor proteins. These include affinity pull-down followed by mass spectrometric analysis. Particularly impressive is the application of DRaCALA-based ORFeome screening (for differential radial capillary action of ligand assay). Here, each protein of a genome is expressed, spotted on a filter and then incubated with nucleotide signalling molecule of interest to determine if the protein affects the radial diffusion of the ligand. Finally, Gerdes [10] (Copenhagen University, Denmark) discussed type I and type II toxin–antitoxin systems and their role in bacterial persister formation. He focused his talk on two general mechanisms—involving either RNases that inhibit translation or type I membrane proteins that induce membrane damage and ATP depletion.

The last session started with a lecture by Cole [11] (EPFL, Ecole polytechnique fédérale de Lausanne, Switzerland) who gave a sobering talk describing the increasing number of multidrug resistant strains of Mycobacterium tuberculosis, the lack of industrial commitment for anti-tuberculosis drug development and other socio-economic factors such as the migration of unvaccinated individuals from different parts of the world, against the background of no EU commitment for funding research on tuberculosis in the framework of Horizon 2020. He also presented work describing an innovative approach to find new drugs that act specifically on intracellular mycobacteria. This led to the identification of a proton pump inhibitor and inhibitors of a key bacterial protein secretion system. Vogel [12] (University of Wurzburg, Germany) described his work on the dual sequencing of RNA of host cells and intracellular bacteria, using Salmonella-infected epithelial cells as a model system. This technical tour de force resulted in the discovery of PinT, a small bacterial RNA which controls expression of virulence proteins involved in invasion and survival of host cells. Furthermore, it seems to have a pleiotropic effect on the host transcriptome, affecting the JAK-STAT immune signalling pathway. Penades [13] (University of Glasgow, Scotland) described a very peculiar form of horizontal gene transfer in Staphylococcus aureus, conferred by phage-inducible chromosomal islands (PICIs). These elements not only direct self-transfer but also control the transfer of unlinked chromosomal virulence genes through an unusual mechanism of transduction. As a result, PICIs appear to be major drivers of adaptation and evolution in several Gram-positive pathogens. The last talk of the meeting was delivered by Sharon Peacock (Bloomsbury Research Institute, London). She discussed the capabilities of the latest generation of benchtop DNA sequencing platforms and their employment in medical practice to investigate hospital outbreaks of bacterial disease and the genetic basis of antibiotic resistance, emphasizing the need to have these platforms in place as a standard resource to help deal with the threat of multidrug resistant pathogens.

The meeting was organized by Pascale Cossart, Steve Busby and David Holden. They chaired sessions together with Richard Moxon and Judith Armitage. It was a stimulating celebration of Bacteriology's new era, built on new techniques including imaging, mass spectrometry and high throughput ’omics approaches, combined with classic biochemistry and genetics.

Competing interests

We declare we have no competing interests.

Funding

We received no funding for this study.