Exploring the principles behind antibiotics with limited resistance

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 21, 2025

Abstract Antibiotics that target multiple cellular functions are anticipated to be less prone bacterial resistance. Here we hypothesize while dual targeting is crucial, it not sufficient in preventing Only those antibiotics simultaneously membrane integrity and block another pathway display reduced resistance development. To test the hypothesis, focus on three antibiotic candidates, POL7306, Tridecaptin M152-P3 SCH79797, all of which fulfill above criteria. show evolution against these limited ESKAPE pathogens, including Escherichia coli , Klebsiella pneumoniae Acinetobacter baumannii Pseudomonas aeruginosa dual-target topoisomerase We discover several mechanisms restricting First, de novo mutations result only a elevation resistance, affecting molecular targets efflux pumps. Second, inaccessible through gene amplification. Third, functional metagenomics reveal mobile genes rare human gut, soil clinical microbiomes. Finally, detect rapid eradication populations upon toxic exposure antibiotics. conclude commonly found natural pathogens provide protection Our work provides guidelines for future development

Language: Английский

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Antimicrobial Resistance in ESKAPE Pathogens: A Retrospective Epidemiological Study at the University Hospital of Palermo, Italy

Antibiotics, Journal Year: 2025, Volume and Issue: 14(2), P. 186 - 186

Published: Feb. 12, 2025

Antimicrobial resistance (AMR) is an escalating global health threat, projected to cause over 40 million deaths by 2050. ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) are major contributors nosocomial infections AMR. We evaluated the epidemiology AMR prevalence of at University Hospital in Palermo between January 2018 July 2023, analyzing factors associated with mortality patients positive blood cultures. Microbiological data from all specimen types were collected using Business Intelligence system Biwer, excluding duplicates. assessed trends isolates time. Clinical hospital discharge forms used evaluate ESKAPE-positive Differences non-blood examined. A total 11,607 specimens 4916 analyzed. Most admitted Internal Medicine (19.4%), ICU (13.2%), General Surgery (9.9%). Additionally, 21.5% ICU-admitted patients. Blood cultures accounted for 14.3% specimens, urine 25.3%, respiratory secretions 22.1%, skin mucosal swabs 20.9%. The increased progressively, peaking 2021. vancomycin-resistant E. faecium was 19.4%, a significant upward trend, while oxacillin-resistant S. aureus 35.0%, showing decline. A. baumannii exhibited high antibiotics tested except colistin cefiderocol. Carbapenemase 55.0% K. 20.4% P. 4.6% spp. aeruginosa showed decrease meropenem resistance. pneumoniae bloodstream linked higher risk.

Language: Английский

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Restoring tigecycline efficacy with lysine supplementation in tmexCD-toprJ-positive bacteria

International Journal of Antimicrobial Agents, Journal Year: 2025, Volume and Issue: unknown, P. 107511 - 107511

Published: April 1, 2025

Language: Английский

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Environmental and clinical impacts of antibiotics’ sub-minimum inhibitory concentrations on the development of resistance in acinetobacter baumannii

The Science of The Total Environment, Journal Year: 2025, Volume and Issue: 979, P. 179521 - 179521

Published: April 27, 2025

Language: Английский

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