Potent Small‐Molecule Suppression of Oxacillin Resistance in Methicillin‐Resistant Staphylococcus aureus

Abstract

The use of adjuvant molecules that have the ability to restore the susceptibility of multi-drug resistant bacteria, such as MRSA, to clinically available antibiotics is a promising alternative to the development of novel antimicrobials. We report an extremely potent small molecule that, at sub-MIC levels, lowers the MIC of oxacillin against a number of MRSA strains by up to 512-fold. Preliminary mechanistic investigations indicate that the VraSR two-component system plays a role in the activity of this compound.

Synergistic Effects Between Thioxanthones and Oxacillin Against Methicillin-ResistantStaphylococcus aureus

“…Therefore, the discovery of non-b-lactams targeting PBP2A 8,41 capable of synergistic activity with existing b-lactams has been widely studied. 16,46 A peptidoglycan analogue (PDB id: 3ZG5) and muramic acid (PDB id: 3ZG0) have been crystallized in the allosteric domain. Muramic acid occurs naturally as an N-acetyl derivative in peptidoglycan, the component of bacterial cell walls.…”

Second generation modifiers of colistin resistance show enhanced activity and lower inherent toxicity

“…In this regard, our group has also recently developed several 2-AIs based upon compound 2 that are capable of reversing β-lactam resistance in methicillin-resistant S. aureus (MRSA). 10,13,14 In these studies, we were able to modify adjuvant activity through imprinting either a 1,4- or 1,5-substitution pattern on the 2-AI ring. Specifically, compound 2 was able to lower the MIC of oxacillin against MRSA fourfold at 25 µM, while from the library of 1,5 substituted derivatives of compound 2 , a compound emerged that is capable of lowering the MIC of oxacillin against MRSA up to 512-fold at 5 µM.…”

“…Specifically, compound 2 was able to lower the MIC of oxacillin against MRSA fourfold at 25 µM, while from the library of 1,5 substituted derivatives of compound 2 , a compound emerged that is capable of lowering the MIC of oxacillin against MRSA up to 512-fold at 5 µM. 10 Inspired by these results, we set out to determine whether imparting either a 1,4- or 1,5-substitution pattern upon the 2-AI of 1 would deliver compounds with augmented activity and reduced inherent toxicity. Herein we report the synthesis of both 1,5- and 1,4-substituted analogues of 1 , as well as the evaluation of their biological activity in terms of colistin resistance suppression.…”

A facile label-free electrochemiluminescent biosensor for specific detection of Staphylococcus aureus utilizing the binding between immunoglobulin G and protein A

“…It exists in most kinds of environments and disseminates rapidly by such media as water, air, food and biological contact, afflicting people worldwide and mostly in developing and underdeveloped countries [1][2][3][4]. Therefore, a reliable, rapid, facile, and low-cost detection technique for S. aureus is urgently demanded for control of infectious diseases.…”