Table 3 BWC0977’s dual-target mechanism demonstrated using engineered E. coli MG1655 gyrA (gyrase) and parC (topoisomerase IV) mutant strains

From: Structural interactions of BWC0977 with Klebsiella pneumoniae topoisomerase IV and biochemical basis of its broad-spectrum activity

Substitution mutation

MIC (μg/mL)

GyrA

ParC

BWC0977

Gepotidacin

Ciprofloxacin

Levofloxacin

Ampicillin

WT

WT

0.03

0.47

0.01

0.03

5

D82N

WT

0.08

0.42

0.08

0.13

5

WT

D79N

0.03

0.83

0.01

0.02

2.5

D82N

D79N

7.5

>40

0.21

0.25

3.3

M120A

M118A

0.0625

0.63

0.01

0.02

4.2

R121K

WT

0.010

0.13

0.08

0.08

4.2

WT

R119K

0.026

0.42

0.021

0.04

5

R121K

R119K

Synthetically lethal/nonviable

  1. The MIC of BWC0977 is shown with E. coli gyrA and parC mutant strains, and compared with gepotidacin, ciprofloxacin, and levofloxacin. Ampicillin is used as a control that does not target either gyrase or topoisomerase IV. The values reported in the table are an average of at least three independent experiments.
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