Global mortality associated with 33 bacterial pathogens in 2019: a systematic analysis for the Global Burden of Disease Study 2019

Plasmids are known to contain genes encoding for virulence factors and antibiotic resistance mechanisms. Their relevance in metagenomic data processing is steadily growing. However, with the increasing popularity and scale of metagenomics experiments, the number of reported plasmids is rapidly growing as well, amassing a considerable number of false positives due to undetected misassembles. Here, our previously published database PLSDB provides a reliable resource for researchers to quickly compare their sequences against selected and annotated previous findings. Within two years, the size of this resource has more than doubled from the initial 13,789 to now 34,513 entries over the course of eight regular data updates. For this update, we aggregated community feedback for major changes to the database featuring new analysis functionality as well as performance, quality, and accessibility improvements. New filtering steps, annotations, and preprocessing of existing records improve the quality of the provided data. Additionally, new features implemented in the web-server ease user interaction and allow for a deeper understanding of custom uploaded sequences, by visualizing similarity information. Lastly, an application programming interface was implemented along with a python library, to allow remote database queries in automated workflows. The latest release of PLSDB is freely accessible under https://www.ccb.uni-saarland.de/plsdb.

https://academic.oup.com/nar/advance-article-pdf/doi/10.1093/nar/gkab1111/41313735/gkab1111.pdf

PLSDB: advancing a comprehensive database of bacterial plasmids.

The history of antimicrobial resistance (AMR) evolution and the diversity of the environmental resistome indicate that AMR is an ancient natural phenomenon. Acquired resistance is a public health concern influenced by the anthropogenic use of antibiotics, leading to the selection of resistant genes. Data show that AMR is spreading globally at different rates, outpacing all efforts to mitigate this crisis. The search for new antibiotic classes is one of the key strategies in the fight against AMR. Since the 1980s, newly marketed antibiotics were either modifications or improvements of known molecules. The World Health Organization (WHO) describes the current pipeline as bleak, and warns about the scarcity of new leads. A quantitative and qualitative analysis of the pre-clinical and clinical pipeline indicates that few antibiotics may reach the market in a few years, predominantly not those that fit the innovative requirements to tackle the challenging spread of AMR. Diversity and innovation are the mainstays to cope with the rapid evolution of AMR. The discovery and development of antibiotics must address resistance to old and novel antibiotics. Here, we review the history and challenges of antibiotics discovery and describe different innovative new leads mechanisms expected to replenish the pipeline, while maintaining a promising possibility to shift the chase and the race between the spread of AMR, preserving antibiotic effectiveness, and meeting innovative leads requirements.

/pdf/antibiotic-discovery-and-resistance-the-chase-and-the-race-1gkuactl.pdf

Antibiotic Discovery and Resistance: The Chase and the Race

Synthesis and characterization of new functionalized chitosan and its antimicrobial and in-vitro release behavior from topical gel.

The emergence of bacterial resistance due to the evolution of microbes under antibiotic selection pressure, and their ability to form biofilm, has necessitated the development of alternative antimicrobial therapeutics. Physical stimulation, as a powerful antimicrobial method to disrupt microbial structure, has been widely used in food and industrial sterilization. With advances in nanotechnology, nanophysical antimicrobial strategies (NPAS) have provided unprecedented opportunities to treat antibiotic‐resistant infections, via a combination of nanomaterials and physical stimulations. In this review, NPAS are categorized according to the modes of their physical stimulation, which include mechanical, optical, magnetic, acoustic, and electrical signals. The biomedical applications of NPAS in combating bacterial infections are systematically introduced, with a focus on their design and antimicrobial mechanisms. Current challenges and further perspectives of NPAS in the clinical treatment of bacterial infections are also summarized and discussed to highlight their potential use in clinical settings. The authors hope that this review will attract more researchers to further advance the promising field of NPAS, and provide new insights for designing powerful strategies to combat bacterial resistance.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/advs.202105252

Nanophysical Antimicrobial Strategies: A Rational Deployment of Nanomaterials and Physical Stimulations in Combating Bacterial Infections

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.

/pdf/towards-the-sustainable-discovery-and-development-of-new-3ugkmuenu2.pdf

Maarten van Dongen

Papers

Towards the sustainable discovery and development of new antibiotics