Title : Adding Insult to Injury: Mechanistic Basis for How AmpC Mutations Allow Pseudomonas aeruginosa To Accelerate Cephalosporin Hydrolysis and Evade Avibactam.

Pub. Date : 2020 Aug 20

PMID : 32660987






12 Functional Relationships(s)
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1 Adding insult to injury: mechanistic basis for how AmpC mutations allow Pseudomonas aeruginosa to accelerate cephalosporin hydrolysis and evade avibactam. Cephalosporins beta-lactamase Pseudomonas aeruginosa PAO1
2 A key mechanism that provides extensive resistance to beta-lactam antibiotics is the inducible expression of AmpC beta-lactamase. beta-Lactams beta-lactamase Pseudomonas aeruginosa PAO1
3 Recently, a number of clinical isolates expressing mutated forms of AmpC have been found to be clinically resistant to the antipseudomonal beta-lactam/beta-lactamase inhibitor (BLI) combinations ceftolozane/tazobactam and ceftazidime/avibactam. beta-Lactams beta-lactamase Pseudomonas aeruginosa PAO1
4 Recently, a number of clinical isolates expressing mutated forms of AmpC have been found to be clinically resistant to the antipseudomonal beta-lactam/beta-lactamase inhibitor (BLI) combinations ceftolozane/tazobactam and ceftazidime/avibactam. ceftolozane beta-lactamase Pseudomonas aeruginosa PAO1
5 Recently, a number of clinical isolates expressing mutated forms of AmpC have been found to be clinically resistant to the antipseudomonal beta-lactam/beta-lactamase inhibitor (BLI) combinations ceftolozane/tazobactam and ceftazidime/avibactam. Tazobactam beta-lactamase Pseudomonas aeruginosa PAO1
6 Recently, a number of clinical isolates expressing mutated forms of AmpC have been found to be clinically resistant to the antipseudomonal beta-lactam/beta-lactamase inhibitor (BLI) combinations ceftolozane/tazobactam and ceftazidime/avibactam. Ceftazidime beta-lactamase Pseudomonas aeruginosa PAO1
7 Recently, a number of clinical isolates expressing mutated forms of AmpC have been found to be clinically resistant to the antipseudomonal beta-lactam/beta-lactamase inhibitor (BLI) combinations ceftolozane/tazobactam and ceftazidime/avibactam. avibactam beta-lactamase Pseudomonas aeruginosa PAO1
8 Second, these mutations reduce the affinity of avibactam for AmpC by increasing the apparent activation barrier of the enzyme acylation step. avibactam beta-lactamase Pseudomonas aeruginosa PAO1
9 It is remarkable that these mutations enhance the catalytic efficiency of AmpC towards ceftolozane and ceftazidime while simultaneously reducing susceptibility to inhibition by avibactam. ceftolozane beta-lactamase Pseudomonas aeruginosa PAO1
10 It is remarkable that these mutations enhance the catalytic efficiency of AmpC towards ceftolozane and ceftazidime while simultaneously reducing susceptibility to inhibition by avibactam. Ceftazidime beta-lactamase Pseudomonas aeruginosa PAO1
11 It is remarkable that these mutations enhance the catalytic efficiency of AmpC towards ceftolozane and ceftazidime while simultaneously reducing susceptibility to inhibition by avibactam. avibactam beta-lactamase Pseudomonas aeruginosa PAO1
12 Knowledge gained from the molecular analysis of these and other AmpC resistance mutants we believe will help aid the design of beta-lactams and BLIs with reduced susceptibility to mutational resistance. beta-Lactams beta-lactamase Pseudomonas aeruginosa PAO1