• Decoding (patho-)physiology of the lung by advanced in vitro models for developing novel anti-infectives therapies.

      Montefusco-Pereira, Carlos Victor; Carvalho-Wodarz, Cristiane de Souza; Seeger, Johanna; Kloft, Charlotte; Michelet, Robin; Lehr, Claus-Michael; HIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany. (Elsevier, 2020-11-21)
      Advanced lung cell culture models provide physiologically-relevant and complex data for mathematical models to exploit host-pathogen responses during anti-infective drug testing.
    • Extracellular vesicles as antigen carriers for novel vaccination avenues.

      Mehanny, Mina; Lehr, Claus-Michael; Fuhrmann, Gregor; HIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany. (Elsevier, 2021-03-26)
      Antigen delivery has always been a challenge in scientific practice of vaccine formulation. Yet, mammalian extracellular vesicles (EVs) or bacterial membrane vesicles (MVs) provide an innovative avenue for safe and effective delivery of antigenic material. They include intrinsically loaded antigens from EV-secreting cells or extrinsically loaded antigens onto pre-formed vesicles. Interestingly, many studies shed light on potential novel anti-cancer vaccination immunotherapy for therapeutic applications from mammalian cell host-derived EVs, as well as conventional vaccination for prophylactic applications using bacterial cell-derived MVs against infectious diseases. Here, we discuss the rationale, status quo and potential for both vaccine applications using EVs.
    • Extracellular vesicles as novel assay tools to study cellular interactions of anti-infective compounds - A perspective.

      Richter, Robert; Lehr, Claus-Michael; HIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany. (Elsevier, 2021-04-20)
      Sudden outbreaks of novel infectious diseases and the persistent evolution of antimicrobial resistant pathogens make it necessary to develop specific tools to quickly understand pathogen-cell interactions and to study appropriate drug delivery strategies. Extracellular vesicles (EVs) are cell-specific biogenic transport systems, which are gaining more and more popularity as either diagnostic markers or drug delivery systems. Apart from that, there are emerging possibilities for EVs as tools to study drug penetration, drug-membrane interactions as well as pathogen-membrane interactions. However, it appears that the potential of EVs for such applications has not been fully exploited yet. Considering the vast variety of cells that can be involved in an infection, vesicle-based analytical methods are just emerging and the number of reported applications is still relatively small. Aim of this review is to discuss the current state of the art of EV-based assays, especially in the context of antimicrobial research and therapy, and to present some new perspectives for a more exhaustive and creative exploration in the future.
    • Mastering the Gram-negative bacterial barrier - Chemical approaches to increase bacterial bioavailability of antibiotics.

      Ropponen, Henni-Karoliina; Richter, Robert; Hirsch, Anna K H; Lehr, Claus Michael; HIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany. (Elsevier, 2021-03-08)
      To win the battle against resistant, pathogenic bacteria, novel classes of anti-infectives and targets are urgently needed. Bacterial uptake, distribution, metabolic and efflux pathways of antibiotics in Gram-negative bacteria determine what we here refer to as bacterial bioavailability. Understanding these mechanisms from a chemical perspective is essential for anti-infective activity and hence, drug discovery as well as drug delivery. A systematic and critical discussion of in bacterio, in vitro and in silico assays reveals that a sufficiently accurate holistic approach is still missing. We expect new findings based on Gram-negative bacterial bioavailability to guide future anti-infective research.
    • Towards the sustainable discovery and development of new antibiotics.

      Miethke, Marcus; Pieroni, Marco; Weber, Tilmann; Brönstrup, Mark; Hammann, Peter; Halby, Ludovic; Arimondo, Paola B; Glaser, Philippe; Aigle, Bertrand; Bode, Helge B; et al. (Springer Nature, 2021-08-19)
      An ever-increasing demand for novel antimicrobials to treat life-threatening infections caused by the global spread of multidrug-resistant bacterial pathogens stands in stark contrast to the current level of investment in their development, particularly in the fields of natural-product-derived and synthetic small molecules. New agents displaying innovative chemistry and modes of action are desperately needed worldwide to tackle the public health menace posed by antimicrobial resistance. Here, our consortium presents a strategic blueprint to substantially improve our ability to discover and develop new antibiotics. We propose both short-term and long-term solutions to overcome the most urgent limitations in the various sectors of research and funding, aiming to bridge the gap between academic, industrial and political stakeholders, and to unite interdisciplinary expertise in order to efficiently fuel the translational pipeline for the benefit of future generations.