β-lactamase expression induces collateral sensitivity in Escherichia coli.

Autor: Herencias C; Servicio de Microbiología, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Hospital Universitario Ramón y Cajal, Madrid, Spain. cherodr@gmail.com.; Centro de Investigación Biomédica en Red de Enfermedades Infecciosas-CIBERINFEC, Instituto de Salud Carlos III, Madrid, Spain. cherodr@gmail.com., Álvaro-Llorente L; Servicio de Microbiología, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Hospital Universitario Ramón y Cajal, Madrid, Spain., Ramiro-Martínez P; Servicio de Microbiología, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Hospital Universitario Ramón y Cajal, Madrid, Spain., Fernández-Calvet A; Centro Nacional de Biotecnología-CSIC, Madrid, Spain., Muñoz-Cazalla A; Servicio de Microbiología, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Hospital Universitario Ramón y Cajal, Madrid, Spain., DelaFuente J; Centro Nacional de Biotecnología-CSIC, Madrid, Spain., Graf FE; Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden.; Centre for Antibiotic Resistance Research (CARe), University of Gothenburg, Gothenburg, Sweden.; Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK., Jaraba-Soto L; Servicio de Microbiología, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Hospital Universitario Ramón y Cajal, Madrid, Spain., Castillo-Polo JA; Servicio de Microbiología, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Hospital Universitario Ramón y Cajal, Madrid, Spain., Cantón R; Servicio de Microbiología, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Hospital Universitario Ramón y Cajal, Madrid, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Infecciosas-CIBERINFEC, Instituto de Salud Carlos III, Madrid, Spain., San Millán Á; Centro Nacional de Biotecnología-CSIC, Madrid, Spain. asanmillan@cnb.csic.es.; Centro de Investigación Biológica en Red de Epidemiología y Salud Pública-CIBERESP, Instituto de Salud Carlos III, Madrid, Spain. asanmillan@cnb.csic.es., Rodríguez-Beltrán J; Servicio de Microbiología, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Hospital Universitario Ramón y Cajal, Madrid, Spain. jeronimo.rodriguez.beltran@gmail.com.; Centro de Investigación Biomédica en Red de Enfermedades Infecciosas-CIBERINFEC, Instituto de Salud Carlos III, Madrid, Spain. jeronimo.rodriguez.beltran@gmail.com.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Jun 03; Vol. 15 (1), pp. 4731. Date of Electronic Publication: 2024 Jun 03.
DOI: 10.1038/s41467-024-49122-2
Abstrakt: Major antibiotic groups are losing effectiveness due to the uncontrollable spread of antimicrobial resistance (AMR) genes. Among these, β-lactam resistance genes -encoding β-lactamases- stand as the most common resistance mechanism in Enterobacterales due to their frequent association with mobile genetic elements. In this context, novel approaches that counter mobile AMR are urgently needed. Collateral sensitivity (CS) occurs when the acquisition of resistance to one antibiotic increases susceptibility to another antibiotic and can be exploited to eliminate AMR selectively. However, most CS networks described so far emerge as a consequence of chromosomal mutations and cannot be leveraged to tackle mobile AMR. Here, we dissect the CS response elicited by the acquisition of a prevalent antibiotic resistance plasmid to reveal that the expression of the β-lactamase gene bla OXA-48 induces CS to colistin and azithromycin. We next show that other clinically relevant mobile β-lactamases produce similar CS responses in multiple, phylogenetically unrelated E. coli strains. Finally, by combining experiments with surveillance data comprising thousands of antibiotic susceptibility tests, we show that β-lactamase-induced CS is pervasive within Enterobacterales. These results highlight that the physiological side-effects of β-lactamases can be leveraged therapeutically, paving the way for the rational design of specific therapies to block mobile AMR or at least counteract their effects.
(© 2024. The Author(s).)
Databáze: MEDLINE
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