LN-1-255, a penicillanic acid sulfone able to inhibit the class D carbapenemase OXA-48.

ABSTRACT:

Objectives

Carbapenemases are the most important mechanism responsible for carbapenem resistance in Enterobacteriaceae. Among carbapenemases, OXA-48 presents unique challenges as it is resistant to β-lactam inhibitors. Here, we test the capacity of the compound LN-1-255, a 6-alkylidene-2'-substituted penicillanic acid sulfone, to inhibit the activity of the carbapenemase OXA-48.

Methods

The OXA-48 gene was cloned and expressed in Klebsiella pneumoniae and Escherichia coli in order to obtain MICs in the presence of inhibitors (clavulanic acid, tazobactam and sulbactam) and LN-1-255. OXA-48 was purified and steady-state kinetics was performed with LN-1-255 and tazobactam. The covalent binding mode of LN-1-255 with OXA-48 was studied by docking assays.

Results

Both OXA-4

SUBMITTER: Vallejo JA 

PROVIDER: S-EPMC4954921 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature