Design and Synthesis of Small Molecules as Potent Staphylococcus aureus Sortase A Inhibitors.

Min Woo Ha,Sung Wook Yi,Seung-Mann Paek

doi:10.3390/antibiotics9100706

Abstract

The widespread and uncontrollable emergence of antibiotic-resistant bacteria, especially methicillin-resistant Staphylococcus aureus, has promoted a wave of efforts to discover a new generation of antibiotics that prevent or treat bacterial infections neither as bactericides nor bacteriostats. Due to its crucial role in virulence and its nonessentiality in bacterial survival, sortase A has been considered as a great target for new antibiotics. Sortase A inhibitors have emerged as promising alternative antivirulence agents against bacteria. Herein, the structural and preparative aspects of some small synthetic organic compounds that block the pathogenic action of sortase A have been described.

Highlights

Antibiotics are indispensable to the health of humankind [1,2,3]
Novel approaches for the development of antibiotics includes targeting virulence via toxin production and virulence factor secretion, impeding bacterial adhesion to host cells and biofilm production and virulence factor secretion, impeding bacterial adhesion to host cells and biofilm formation, interrupting or inhibiting bacterial communication, and downregulating virulence
As of the struggle against drug resistance, the development of sortase A inhibitor has emerged as an part of the struggle against drug resistance, the development of sortase A inhibitor has emerged as alternative to conventional antibiotics, with a mechanism that involves blocking the pathogenic an alternative to conventional antibiotics, with a mechanism that involves blocking the pathogenic processes of bacterial infection

Summary

Introduction

Antibiotics are indispensable to the health of humankind [1,2,3]. Owing to the great contribution of commendable antibiotics, we might expect to extend our life expectancy over the age of 50 without substantial difficulties. Antibiotics deactivate bacterial infections by directly killing the bacteria and/or blocking its growth, preventing its spread [4]. The greatest concerns regarding antibiotic-resistant bacteria, especially methicillin resistant Staphylococcus aureus (MRSA). For several difficult-to-treat infections in humans such as pneumonia, bacteremia, osteomyelitis, and endocarditis [10,11], resulted in the development of a new generation of antibiotics that target the alternative enzyme components, fighting bacterial infections not as bactericides or bacteriostats [12,13].

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Conclusion