Discovery of Novel UDP--Acetylglucosamine Acyltransferase (LpxA) Inhibitors with Activity against .

This study describes a novel series of UDP--acetylglucosamine acyltransferase (LpxA) inhibitors that was identified through affinity-mediated selection from a DNA-encoded compound library. The original hit was a selective inhibitor of LpxA with no activity against LpxA. The biochemical potency of the series was optimized through an X-ray crystallography-supported medicinal chemistry program, resulting in compounds with nanomolar activity against LpxA (best half-maximal inhibitory concentration (IC) <5 nM) and cellular activity against (best minimal inhibitory concentration (MIC) of 4 μg/mL).

Effect of Susceptibility Testing Conditions on the In Vitro Antibacterial Activity of ETX0914.

The effect of various conditions including pH, inoculum, temperature, atmosphere, divalent cations, and several body fluids on the in vitro activity of the novel antibacterial spiropyrimidinetrione ETX0914 in standard susceptibility tests was investigated against several species. None of the parameters investigated affected the activity of ETX0914, with the exception of pH. Whereas the MIC values for ETX0914 with S.

Molecular mechanisms of sulbactam antibacterial activity and resistance determinants in Acinetobacter baumannii.

Sulbactam is a class A β-lactamase inhibitor with intrinsic whole-cell activity against certain bacterial species, including Acinetobacter baumannii. The clinical use of sulbactam for A. baumannii infections is of interest due to increasing multidrug resistance in this pathogen.