Prof. Jan-Willem Veening Department of Fundamental Microbiology, UNIL, Switzerland
“Collective resistance in microbial communities by intracellular antibiotic deactivation”
The structure and composition of bacterial communities can compromise antibiotic efficacy. For example, the secretion of β-lactamase by individual bacteria provides passive resistance for all residents within a polymicrobial environment. Here, we uncover that collective resistance can also develop via intracellular antibiotic deactivation. Real-time luminescence measurements and single-cell analysis demonstrate that the human pathogen Streptococcus pneumoniae grows in medium supplemented with chloramphenicol when resistant bacteria expressing chloramphenicol acetyltransferase (CAT) are present. We show that CAT processes chloramphenicol intracellularly but not extracellularly. In a mouse pneumonia model, more susceptible pneumococci survive chloramphenicol treatment when co-infected with a CAT-expressing strain. Mathematical modeling predicts that stable coexistence is only possible when antibiotic resistance comes at a fitness cost. Strikingly, CAT-expressing pneumococci in mouse lungs were outcompeted by susceptible cells even during chloramphenicol treatment. Our results highlight the importance of the microbial context during infectious disease as a potential complicating factor to antibiotic therapy.
Prof. Thomas Speck Plant Biomechanics Group Freiburg, Botanic Garden, University of Freiburg, Germany
“Bioinspired solutions for architecture and building construction”
During the last decades biomimetics has attracted increasing attention as well from basic and applied research as from various fields of industry, architecture and especially from building construction. Biomimetics has a high innovation potential and offers the possibility for the development of sustainable technical products and production chains. The huge number of organisms with the specific structures and functions they have developed during evolution in adaptation to differing environments represents the basis for all biomimetic R&D-projects. Novel sophisticated methods for quantitatively analysing and simulating the form-structure-function-relationship on various hierarchical levels allow new fascination insights in multi-scale mechanics and other functions of biological materials and surfaces. On the other hand, new production methods enable for the first time the transfer of many outstanding properties of the biological role models into innovative biomimetic products for reasonable costs. Within the framework of the new Collaborative Research Centre CRC 141 “Biological Design and Integrative Structures” an interdisciplinary team aims to explore the potential of biomimetics for a new smart kind of bioinspired architecture.
After a short introduction into the topic, the interdisciplinary approach and the different process sequences for the development of biomimetic materials for building construction are presented. Main focus is laid on bioinspired light-weight and damping materials and structures as well as on self-x-materials. Examples include branched fiber-reinforced light-weight composite materials, structural materials with a high energy dissipation capacity as fiber-reinforced graded foams and thin-layer compound materials, bioinspired anti-adhesive materials and surfaces, bioinspired self-repairing structural materials, and the biomimetic façade-shading systems flectofin® and flectofold inspired by the bird of paradise flower and the waterwheel plant, respectively.
Prof. Christel Vérollet Institute of Pharmacology and Structural Biology, Toulouse, France
“Role of macrophages in HIV-1 pathogenesis and in the context of co-infection with Tuberculosis”
In addition to T lymphocytes, macrophages are infected by HIV-1 and make important contribution to AIDS pathogenesis (1-4). We have shown that HIV-1 reprograms macrophage migration (3), which likely explains macrophage accumulation in several patient tissues, a key step for virus dissemination and pathogenesis. Tuberculosis (TB) is the most common opportunistic infection and cause of mortality among HIV+ patients, especially in resource-limited countries. At the heart of this problem is the synergy between HIV-1 and Mycobacterium Tuberculosis (Mtb), the agent responsible for TB, which impacts the pathogenesis of one another (5). While CD4+ T cell decay is a well-known leading cause for reactivation of latent TB and disease progression in AIDS patients, the mechanisms explaining how Mtb amplifies HIV-1 pathogenesis remain scarce.
We recently showed that TB drives human monocyte differentiation towards an M(IL-10) macrophage activation program whose in vivo abundance correlates with TB severity (6). Here, we examined whether these M(IL-10) macrophages play a role in HIV-1 infection as a direct consequence of the effect imparted by TB.
Using two independent models to mimic a TB-derived microenvironment, we show that HIV-1 production becomes exacerbated in M(IL-10) macrophages, along with high formation of multinucleated giant cells and cell motility, which both favor viral dissemination (4). Importantly, we demonstrate the accumulation of M(IL-10) cells in blood of co-infected patients and lung of co-infected non-human primates. Finally, we demonstrate the critical role for the IL-10/STAT3 axis in rendering macrophages highly susceptible to HIV-1 infection via the formation of tunneling nanotubes which favors viral spread. Altogether, our results propose M(IL-10) macrophages as key players in the amplifying effect of TB on HIV pathogenesis.
This work further supports the growing interest in macrophages as potential reservoirs for persistent HIV-1 infection and as potential targets with therapeutic activity in HIV and co-infected patients.
(1) Honeycutt JB et al., J Clin Invest. 2016
(2) Vérollet C et al., J Immunol. 2010
(3) Vérollet C et al., Blood. 2014
(4) Vérollet et al., Frontiers in Immunol. 2015
(5) Diedrich CR and Flynn JL, Infect Immun. 2011
(6) Lastrucci C et al., Cell Research, 2015
Prof. Daniel Durstewitz Department of Theoretical Neuroscience, Central Institute of Mental Health Mannheim/Heidelberg University, Germany
“The Quest for the Neural Code”
The quintessence of neuronal communication are the action potentials or “spikes”, sharp pulse-like electrical events that neurons send down their axons to evoke postsynaptic potentials in connected cells. All information our brains have about the external world, and all internal mental events, must ultimately be represented in the spatio-temporal patterns of spiking activity. For many decades now neuroscientists have been exploring various ideas about how information may be encoded by the neurons’ spiking activity, but for long progress has been hampered by mainly two factors: 1) Experimentally, usually only a small number of neurons could be recorded from simultaneously with sufficient temporal resolution. 2) Computationally, the combinatorial explosion problem inherent in scanning multiple spike trains for spatio-temporal patterns limited the search to only a few candidate patterns defined by the experimenter’s hypotheses.
This recently changed with the advancement of multiple single-unit recording techniques, enabling simultaneous access to up to hundreds of cells, and the recent rapid progress in machine learning methods. Harvesting such methods, it became recently feasible to explore all potential coding schemes from a huge space of possibilities, in an unbiased, hypothesis-free manner, across multiple time scales. My talk will be centered on these recent developments.
- J. Wellbourne-Wood, “Imaging extracellular potassium dynamic in brain tissue using a potassium-sensitive nano sensor”
- A. Balso, “Role of Th17 vs neutrophil-derived IL-26 in skin inflammation”
- I. Labgaa, “Ultra-deep sequencing of plasma DNA identifies draggable mutations in hepatocellular carcinoma”
- A. Vucicevic, “Characterization of a large 14-kb operon involved in conjugative transfer of ICEclc of Pseudomonas knackmussii B13”
- T.G. Andersen, “The root passage cell – Just another brick in the wall?”
- E. Durandau, “Dynamic measurement of kinase activity in live single cell”