Collateral Sensitivity Constrains Resistance Evolution Of The CTX-M-15 β-lactamase

Condensed Matter journal club

Collateral Sensitivity Constrains Resistance Evolution Of The CTX-M-15 β-lactamase

  • Event time: 11:30am until 12:30pm
  • Event date: 22nd February 2019
  • Speaker: (School of Physics & Astronomy, University of Edinburgh)
  • Location: 2511

Event details

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 β-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.

Event resources

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Given the diversity of research in the CM group, chosen topics vary widely. We tend to stick to high-impact journals - Nature, Science, PNAS and PRL have been popular - but this is not prescriptive..

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