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β-lactamase express...
β-lactamase expression induces collateral sensitivity in Escherichia coli
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Herencias, Cristina (författare)
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Alvaro-Llorente, Laura (författare)
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Ramiro-Martinez, Paula (författare)
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Fernandez-Calvet, Ariadna (författare)
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Munoz-Cazalla, Ada (författare)
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DelaFuente, Javier (författare)
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- Graf, Fabrice (författare)
- Gothenburg University,Göteborgs universitet,CARe - Centrum för antibiotikaresistensforskning,Institutionen för kemi och molekylärbiologi,Centre for antibiotic resistance research, CARe,Department of Chemistry and Molecular Biology
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Jaraba-Soto, Laura (författare)
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Castillo-Polo, Juan Antonio (författare)
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Canton, Rafael (författare)
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San Millan, Alvaro (författare)
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Rodriguez-Beltran, Jeronimo (författare)
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(creator_code:org_t)
- 2024
- 2024
- Engelska.
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Ingår i: NATURE COMMUNICATIONS. - 2041-1723. ; 15:1
- Relaterad länk:
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Major antibiotic groups are losing effectiveness due to the uncontrollable spread of antimicrobial resistance (AMR) genes. Among these, beta-lactam resistance genes -encoding beta-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 beta-lactamase gene bla OXA-48 induces CS to colistin and azithromycin. We next show that other clinically relevant mobile beta-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 beta-lactamase-induced CS is pervasive within Enterobacterales. These results highlight that the physiological side-effects of beta-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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
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Herencias, Crist ...
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Alvaro-Llorente, ...
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Ramiro-Martinez, ...
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Fernandez-Calvet ...
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Munoz-Cazalla, A ...
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DelaFuente, Javi ...
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visa fler...
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Graf, Fabrice
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Jaraba-Soto, Lau ...
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Castillo-Polo, J ...
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Canton, Rafael
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San Millan, Alva ...
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Rodriguez-Beltra ...
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Infektionsmedici ...
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NATURE COMMUNICA ...
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Göteborgs universitet