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Collateral sensitiv...
Collateral sensitivity constrains resistance evolution of the CTX-M-15 beta-lactamase
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- Rosenkilde, Carola E. H. (författare)
- Tech Univ Denmark, Novo Nordisk Fdn Ctr Biosustainabil, DK-2800 Lyngby, Denmark
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- Munck, Christian (författare)
- Tech Univ Denmark, Novo Nordisk Fdn Ctr Biosustainabil, DK-2800 Lyngby, Denmark;Columbia Univ, Dept Syst Biol, New York, NY USA
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- Porse, Andreas (författare)
- Tech Univ Denmark, Novo Nordisk Fdn Ctr Biosustainabil, DK-2800 Lyngby, Denmark
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- Linkevicius, Marius (författare)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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- Andersson, Dan I (författare)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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- Sommer, Morten O. A. (författare)
- Tech Univ Denmark, Novo Nordisk Fdn Ctr Biosustainabil, DK-2800 Lyngby, Denmark
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(creator_code:org_t)
- 2019-02-06
- 2019
- Engelska.
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 10
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://www.nature.c...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
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- Antibiotic resistance is a major challenge to global public health. Discovery of new antibiotics is slow and to ensure proper treatment of bacterial infections new strategies are needed. One way to curb the development of antibiotic resistance is to design drug combinations where the development of resistance against one drug leads to collateral sensitivity to the other drug. Here we study collateral sensitivity patterns of the globally distributed extended-spectrum beta-lactamase CTX-M-15, and find three non-synonymous mutations with increased resistance against mecillinam or piperacillin-tazobactam that simultaneously confer full susceptibility to several cephalosporin drugs. We show in vitro and in mice that a combination of mecillinam and cefotaxime eliminates both wild-type and resistant CTX-M-15. Our results indicate that mecillinam and cefotaxime in combination constrain resistance evolution of CTX-M-15, and illustrate how drug combinations can be rationally designed to limit the resistance evolution of horizontally transferred genes by exploiting collateral sensitivity patterns.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
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