bioRxiv Science⌕ Search

bioRxiv · 10.1101/2021.03.01.433375

Mapping Twenty Years of Antimicrobial Resistance Research Trends

Abstract

BackgroundAntimicrobial resistance (AMR) is a global threat to health and healthcare. In response to the growing AMR burden, research funding also increased. However, a comprehensive overview of the research output, including conceptual, temporal, and geographical trends, is missing. Therefore, this study uses topic modelling, a machine learning approach, to reveal the scientific evolution of AMR research and its trends, and provides an interactive user interface for further analyses. MethodsStructural topic modelling (STM) was applied on a text corpus resulting from a PubMed query comprising AMR articles (1999-2018). A topic network was established and topic trends were analysed by frequency, proportion, and importance over time and space. FindingsIn total, 88 topics were identified in 158616 articles from 166 countries. AMR publications increased by 450% between 1999 and 2018, emphasizing the vibrancy of the field. Prominent topics in 2018 were Strategies for emerging resistances and diseases, Nanoparticles, and Stewardship. Emerging topics included Water and environment, and Sequencing. Geographical trends showed prominence of Multidrug-resistant tuberculosis (MDR-TB) in the WHO African Region, corresponding with the MDR-TB burden. China and India were growing contributors in recent years, following the United States of America as overall lead contributor. InterpretationThis study provides a comprehensive overview of the AMR research output thereby revealing the AMR research response to the increased AMR burden. Both the results and the publicly available interactive database serve as a base to inform and optimise future research. FundingINTERREG-VA EurHealth-1Health (202085); European Commission Horizon 2020 Framework Research in contextO_ST_ABSEvidence before this studyC_ST_ABSPrior to this study, PubMed, Web of Science, Scopus, and IEEE Xplore were queried to find studies providing a conceptual overview of antimicrobial resistance (AMR) research over time and space. The search string included keywords ("antimicrobial" OR antibiotic*) AND (resistan*) AND ("science mapping" OR bibliometric OR scientometric) in the title and abstract and focused on articles published before 2019 without language restrictions. Few studies were found relying on scientometric and bibliometric methods to assess either subfields of AMR research (e.g., AMR among uropathogens) or AMR-related fields (e.g., microbiology). No studies were found that focus on the entire AMR field. Therefore, this science mapping study using topic modelling was performed to provide an overview of the AMR field by identifying and assessing topics, trends, and geographical differences over time. Added value of this studyTo the best of our knowledge, this study is the first to use a science mapping approach to provide a comprehensive overview of the entire AMR research field, covering over 150 thousand articles published between 1999 and 2018. Our findings revealed important (e.g., Strategies for emerging resistances and diseases, Nanoparticles, and Stewardship) and emerging (e.g., Water and environment, and Sequencing) topics in AMR research. Lastly, this study resulted in an interactive user interface where all data are presented for further analyses. Implications of all the available evidenceOur comprehensive overview of the AMR field, including its conceptual structure, and temporal and geographical trends revealed the response of the research community to the AMR burden. The results and the openly available supporting data provide the base to guide future funding and research directions to tackle AMR.

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Luz, C. F., van Niekerk, M., Keizer, J., Beerlage-de Jong, N., Braakman-Jansen, A., Stein, A., Sinha, B., van Gemert-Pijnen, L., Glasner, C.. 2021-03-01. Mapping Twenty Years of Antimicrobial Resistance Research Trends. https://doi.org/10.1101/2021.03.01.433375

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

Microbially conjugated bile acids differentially affect the lifecycle and pathogenesis of Clostridioides difficile

Clostridioides difficile is a Gram-positive bacterium that causes C. difficile infection (CDI). In healthy adults, it has been proposed that the gut microbiota provides colonization resistance against C. difficile by competition through nutrient limitation and antagonism through secondary bile acid metabolism, the latter of which is mediated by the deconjugation of host-derived bile acids with bacterial bile salt hydrolases (BSH). Recently, BSHs have also shown an ability to reconjugate non-canonical (i.e., not glycine or taurine) amino acids to sterol cores, resulting in novel microbially conjugated bile acids (MCBAs). MCBAs have been associated with the resolution of recurrent CDI, though the mechanism underlying these effects are not well understood. To address this gap, we synthesized 36 MCBAs with nine amino acids (cysteine, isoleucine, leucine, phenylalanine, proline, serine, tryptophan, tyrosine, and valine) conjugated to the primary and secondary bile acids found in the human gut (CA, DCA, CDCA, and LCA) and tested their impact on various stages of C. difficiles lifecycle including bacterial outgrowth, membrane integrity, sporulation, and toxin activity. We show that BSH-mediated amidation of bile acid sterol cores can either increase or decrease inhibitory effects on C. difficile in an amino acid-dependent manner. For example, serine MCBAs enhanced C. difficiles ability to grow in otherwise inhibitory bile acid concentrations, increased spore production, and elevated toxin activity. Tryptophan MCBAs increased inhibition. By demonstrating these variable effects, our work clarifies the molecular determinants of MCBA activity and highlights specific MCBAs as promising targets for the development of C. difficile microbial-based therapeutics.

microbiology↗

Magnetic organelle gene clusters enable bacterial growth and ATP homeostasis under oxidizing conditions

Biological organisms can produce magnetic nanoparticles made of magnetite to detect the Earth's magnetic field for orientation. The evolutionary mechanisms that led to the acquisition of this capacity remain unknown. The most ancient organisms known to perform magnetic orientation are magnetotactic bacteria. Under tight genetic control, they produce chains of magnetite nanoparticles in dedicated organelles to allow efficient navigation in aquatic environments containing molecular oxygen. Yet, these bacteria have been proposed to emerge before molecular oxygen became abundant on Earth, at a time when this navigation system could not have served its current function. Here, we show that gene clusters responsible of magnetite formation and organization enable resistance against hydrogen peroxide, a toxic oxygen-derived compound that was produced during the early stages of Earth's oxygenation when iron oxidation consumed molecular oxygen. Characterization of the nanoparticle's oxidation state supported the involvement of magnetite in resistance to hydrogen peroxide-induced oxidative stress. These findings are compatible with an early emergence of magnetotactic bacteria, before natural waters became oxygenated. We propose a conceptual framework to explain the origin of magnetic orientation in bacteria, and offer tools to identify the initiation of Earth's oxygenation in a time-resolved manner.

microbiology↗

Identification and characterization of new P. aeruginosa phages using a surface receptor platform

Bacteriophages are of increasing interest for their potential use as alternatives to antibiotics for treating drug-resistant infections. Phage steering, specifically receptor-based steering, involves use of phages that bias the development of resistance in bacteria towards phenotypes such as reduced fitness. Phage therapy typically involves administering cocktails of phages with different targets to reduce the likelihood of resistance emerging. To ensure effective steering and cocktail design, there is a need to identify the receptors used by phages of interest, and to isolate phages that use diverse receptors. Here we describe a SURFAce Receptor (SURFAR) platform consisting of a set of defined Pseudomonas aeruginosa strains and mutants for rapid characterization of phage receptors. This platform can also be used to enrich for and isolate diverse phages from environmental samples, yielding novel phage genomes from wastewater. Using the SURFAR platform, two new phages were isolated and characterized: Dalewood, which targets both flagella and the conserved LPS outer core, and Bowman, a biofilm targeting phage capable of supressing growth of a subset of carbapenem-resistant clinical isolates. This tool helps to standardize the laborious but important task of phage receptor characterization, with the goal of expanding the known repertoire of P. aeruginosa phage receptors and phages.

microbiology↗