<i>Staphylococcus aureus</i> selective antimicrobial polymers based on an arginine‐derived monomer

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Abstract

The continuous spread of resistance genes among bacterial populations, in particular in hospital setting, threatens the advances of our medical systems and already costs more than 1 million lives per year. Antimicrobial polymers (APs) are a promising type of materials to counteract these developments, as they are non‐susceptible toward resistance development, and even target resistant bacteria. We herein show the synthesis of an arginine‐containing monomer and its polymerization via photo‐induced reversible addition‐fragmentation chain‐transfer polymerization. The synthesis is straightforward, and the macromolecules possess two charged functions (i.e., guanidinium and ammonium) per repeating unit after deprotection. Assessment of the biological activity reveals that polymers inhibit the growth of methicillin‐resistant Staphylococcus aureus (MRSA) while being relatively inactive against tested Gram‐negative strains. Surprisingly, among the tested polymers, the homopolymer of the arginine‐derived monomer is the best‐performing material, even though it possesses no notable hydrophobic units. Toxicity tests against red blood cells and other mammalian cells show a good biocompatibility of polymers, leading to an overall excellent selectivity. Using membrane models, the mechanism of action was found to be membrane disruption. The good selectivity of the herein presented polymer for MRSA makes them promising materials for the development of therapeutic agents against such infections.

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Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis

(2022)

Summary Background Antimicrobial resistance (AMR) poses a major threat to human health around the world. Previous publications have estimated the effect of AMR on incidence, deaths, hospital length of stay, and health-care costs for specific pathogen–drug combinations in select locations. To our knowledge, this study presents the most comprehensive estimates of AMR burden to date. Methods We estimated deaths and disability-adjusted life-years (DALYs) attributable to and associated with bacterial AMR for 23 pathogens and 88 pathogen–drug combinations in 204 countries and territories in 2019. We obtained data from systematic literature reviews, hospital systems, surveillance systems, and other sources, covering 471 million individual records or isolates and 7585 study-location-years. We used predictive statistical modelling to produce estimates of AMR burden for all locations, including for locations with no data. Our approach can be divided into five broad components: number of deaths where infection played a role, proportion of infectious deaths attributable to a given infectious syndrome, proportion of infectious syndrome deaths attributable to a given pathogen, the percentage of a given pathogen resistant to an antibiotic of interest, and the excess risk of death or duration of an infection associated with this resistance. Using these components, we estimated disease burden based on two counterfactuals: deaths attributable to AMR (based on an alternative scenario in which all drug-resistant infections were replaced by drug-susceptible infections), and deaths associated with AMR (based on an alternative scenario in which all drug-resistant infections were replaced by no infection). We generated 95% uncertainty intervals (UIs) for final estimates as the 25th and 975th ordered values across 1000 posterior draws, and models were cross-validated for out-of-sample predictive validity. We present final estimates aggregated to the global and regional level. Findings On the basis of our predictive statistical models, there were an estimated 4·95 million (3·62–6·57) deaths associated with bacterial AMR in 2019, including 1·27 million (95% UI 0·911–1·71) deaths attributable to bacterial AMR. At the regional level, we estimated the all-age death rate attributable to resistance to be highest in western sub-Saharan Africa, at 27·3 deaths per 100 000 (20·9–35·3), and lowest in Australasia, at 6·5 deaths (4·3–9·4) per 100 000. Lower respiratory infections accounted for more than 1·5 million deaths associated with resistance in 2019, making it the most burdensome infectious syndrome. The six leading pathogens for deaths associated with resistance (Escherichia coli, followed by Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa) were responsible for 929 000 (660 000–1 270 000) deaths attributable to AMR and 3·57 million (2·62–4·78) deaths associated with AMR in 2019. One pathogen–drug combination, meticillin-resistant S aureus, caused more than 100 000 deaths attributable to AMR in 2019, while six more each caused 50 000–100 000 deaths: multidrug-resistant excluding extensively drug-resistant tuberculosis, third-generation cephalosporin-resistant E coli, carbapenem-resistant A baumannii, fluoroquinolone-resistant E coli, carbapenem-resistant K pneumoniae, and third-generation cephalosporin-resistant K pneumoniae. Interpretation To our knowledge, this study provides the first comprehensive assessment of the global burden of AMR, as well as an evaluation of the availability of data. AMR is a leading cause of death around the world, with the highest burdens in low-resource settings. Understanding the burden of AMR and the leading pathogen–drug combinations contributing to it is crucial to making informed and location-specific policy decisions, particularly about infection prevention and control programmes, access to essential antibiotics, and research and development of new vaccines and antibiotics. There are serious data gaps in many low-income settings, emphasising the need to expand microbiology laboratory capacity and data collection systems to improve our understanding of this important human health threat. Funding Bill & Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care using UK aid funding managed by the Fleming Fund.

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Methicillin-resistant Staphylococcus aureus: an overview of basic and clinical research

Nicholas A Turner, Batu K. Sharma-Kuinkel, Stacey A Maskarinec … (2019)

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most successful modern pathogens. The same organism that lives as a commensal and is transmitted in both health-care and community settings is also a leading cause of bacteraemia, endocarditis, skin and soft tissue infections, bone and joint infections and hospital-acquired infections. Genetically diverse, the epidemiology of MRSA is primarily characterized by the serial emergence of epidemic strains. Although its incidence has recently declined in some regions, MRSA still poses a formidable clinical threat, with persistently high morbidity and mortality. Successful treatment remains challenging and requires the evaluation of both novel antimicrobials and adjunctive aspects of care, such as infectious disease consultation, echocardiography and source control. In this Review, we provide an overview of basic and clinical MRSA research and summarize the expansive body of literature on the epidemiology, transmission, genetic diversity, evolution, surveillance and treatment of MRSA.

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Methicillin-resistant Staphylococcus aureus

Andreas Peschel, Surbhi Malhotra-Kumar, Jan Kluytmans … (2018)

Since the 1960s, methicillin-resistant Staphylococcus aureus (MRSA) has emerged, disseminated globally and become a leading cause of bacterial infections in both health-care and community settings. However, there is marked geographical variation in MRSA burden owing to several factors, including differences in local infection control practices and pathogen-specific characteristics of the circulating clones. Different MRSA clones have resulted from the independent acquisition of staphylococcal cassette chromosome mec (SCCmec), which contains genes encoding proteins that render the bacterium resistant to most β-lactam antibiotics (such as methicillin), by several S. aureus clones. The success of MRSA is a consequence of the extensive arsenal of virulence factors produced by S. aureus combined with β-lactam resistance and, for most clones, resistance to other antibiotic classes. Clinical manifestations of MRSA range from asymptomatic colonization of the nasal mucosa to mild skin and soft tissue infections to fulminant invasive disease with high mortality. Although treatment options for MRSA are limited, several new antimicrobials are under development. An understanding of colonization dynamics, routes of transmission, risk factors for progression to infection and conditions that promote the emergence of resistance will enable optimization of strategies to effectively control MRSA. Vaccine candidates are also under development and could become an effective prevention measure.

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Author and article information

Contributors

Johannes Gurke: (View ORCID Profile)

Meike N. Leiske: (View ORCID Profile)

Matthias Hartlieb: (View ORCID Profile)

Journal

Title: Journal of Polymer Science

Abbreviated Title: Journal of Polymer Science

Publisher: Wiley

ISSN (Print): 2642-4150

ISSN (Electronic): 2642-4169

Publication date Created: January 2024

Publication date (Electronic): October 25 2023

Publication date (Print): January 2024

Volume: 62

Issue: 1

Pages: 132-145

Affiliations

[1 ] Institute of Chemistry, University of Potsdam Potsdam Germany

[2 ] Fraunhofer Institute for Applied Polymer Research (IAP) Potsdam Germany

[3 ] Faculty of Biology, Chemistry & Earth Sciences University of Bayreuth Bayreuth Germany

[4 ] Bavarian Polymer Institute (BPI), University of Bayreuth Bayreuth Germany

Article

DOI: 10.1002/pol.20230591

SO-VID: db409450-654d-4808-b37f-b0e3413744c7

License:

http://creativecommons.org/licenses/by-nc/4.0/

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