Anti-virulence to Counter the AMR Conundrum: Principles and Strategies

Abstract

Antibiotic resistance for a large diversity of clinically significant pathogens has been observed with increasing frequency over the past several decades. This pervasive issue is one of the most serious public health concerns of this century. Clinicians and researchers have been persuaded to develop innovative techniques to manage harmful microorganisms to address this problem. The bacterial virulence genes are mostly in the monitoring purview of quorum sensing signal molecules, called autoinducers, and are expressed only when the signal is beyond a threshold which is determined by the bacterial cell density. Hence, interfering with these signals will effectively silence the operon that harbors virulence genes, without being detrimental to bacteria so that there is no selective pressure. This interpolation with quorum sensing paths of microbes, known as antipathogenic and/or anti-virulence strategies, is one of several such promising approaches which mainly focus on disruption of bacterial pathogenicity and does not involve bacterial killing. Inhibition of indicator molecules is accomplished by signal dilapidation, use of natural or synthetic analogues, and various other strategies which are described in this chapter. Also discussed are the modes of action of bacterial quorum sensing and an overview of potential sources of bioactive components as QS inhibitors.