Anti-quorum Sensing Therapies: Issues and Limitations

Quorum sensing (QS) is a technique that allows bacteria to detect population density and control gene expression simultaneously. The proliferation of multidrug-resistant (MDR) bacteria has become a serious public health concern around the world. Thus, novel ways to treat bacterial infections caused by MDR strains of species such as Pseudomonas aeruginosa and Acinetobacter baumannii are urgently needed. In bacterial communities, QS is an important communication system that regulates survival and virulence. QS inhibitors have led to the study of the importance of QS in bacterial infections. Many important microbial pathogenic activities, such as sporulation, biofilm development and enzyme/vesicle secretion, are regulated by QS. This resulted in the development of anti-QS therapy [or quorum quenching (QQ)] to combat infections. It has been shown that combining bacteria with antibiotics can reduce pathogenicity. The purpose of this paper is to highlight the unfavorable aspects of QQ therapy, with a focus on three essential features attributed to anti-QS substances: selectivity, decreased virulence and lack of resistance to QQ. Resistance mechanisms to various types of quorum quenchers, such as signal-degrading enzymes, such as lactonases or acylases for homoserine lactone (HSL) autoinducers, are discussed. This perspective may reveal areas of further study and also shows additional research directions that should be considered in the future before QQ treatments are widely used in the treatment of humans.