NH125 Sensitizes Staphylococcus aureus to Cell Wall-Targeting Antibiotics through the Inhibition of the VraS Sensor Histidine Kinase

Abstract

This work characterizes the activity and inhibition of VraS, which is a key histidine kinase in a bacterial two-component system that is involved in Staphylococcus aureus antibiotic resistance. The results show the effect of temperature, divalent ions, and VraR on the activity and the kinetic parameters of ATP binding.

The Staphylococcus aureus ArlS Kinase Inhibitor Tilmicosin Has Potent Anti-Biofilm Activity in Both Static and Flow Conditions

“…Previous studies in our laboratory have discovered novel compounds targeting S. epidermidis essential YycG histidine kinase CA domain, which have potent inhibitory effects on staphylococcal growth and biofilm formation [ 74 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 ]. Recently, there has been inspiring progress on the development of novel inhibitors against several other HKs, including S. aureus VraS (involved in cell call-targeting antibiotics susceptibility) [ 94 ], AgrC (important for quorum sensing and virulence regulation) [ 95 ], etc. In addition, the extracellular domain of HK is responsible for sensing environment signals, so it may also serve as a potential target for screening inhibitory peptides or monoclonal antibodies (mAbs) that can block signal recognition [ 96 , 97 ].…”