Evolution of Resistance to Quorum-Sensing Inhibitors

Abstract

The major cause of mortality and morbidity in human beings is bacterial infection. Bacteria have developed resistance to most of the antibiotics primarily due to large scale and “indiscriminate” usage. The need is to develop novel mechanisms to treat bacterial infections. The expression of pathogenicity during bacterial infections is mediated by a cell density dependent phenomenon known as quorum sensing (QS). A wide array of QS systems (QSS) is operative in expressing the virulent behavior of bacterial pathogens. Each QSS may be mediated largely by a few major signals along with others produced in minuscule quantities. Efforts to target signal molecules and their receptors have proved effective in alleviating the virulent behavior of such pathogenic bacteria. These QS inhibitors (QSIs) have been reported to be effective in influencing the pathogenicity without affecting bacterial growth. However, evidence is accumulating that bacteria may develop resistance to QSIs. The big question is whether QSIs will meet the same fate as antibiotics?

Bacterial Virulence Factors: Secreted for Survival

“…Since, the secreted factors can be effectively targeted by therapeutic molecules or vaccines, an in-depth understanding of their role in virulence will assist in identification of the 'right factors' which are most crucial for the pathogen's survival. Apart from secreted proteins, pathogens also secrete small molecule or quorum sensing molecules, which are important for the pathogen to establish infection and the role of these molecules has been well studied in pathogenic as well as non-pathogenic bacteria [68][69][70][71][72][73]. This review enhance our understanding about the crucial roles played by the secreted virulence factor of Mtb and B. anthracis.…”

Potential Emergence of Multi-quorum Sensing Inhibitor Resistant (MQSIR) Bacteria

“…Plasmid transfer [77] Acinetobacter baumannii AbaI/AbaR C12HSL, C10HSL, C14HSL, C16HSL, 3OC13HSL, OHC12HSL Biofilm formation and surface motility; virulence; production of antioxidant enzymes-catalase and superoxide dismutase [134] Brucella melitensis VjbR, BlxR (orphan LuxR homologs) C12HSL, 3OC12HSL Surface modifications by regulating flagellar genes and type IV secretion system genes (virulence) [133] Hafnia alvei Modulate expression of virulence genes [140] Xanthomonas campestris DSF signalling system DSF (diffusible signal factor): cis-11-methyl-2-dodecanoic acid Regulation of virulence [142] a Quorum sensing system 1920's, has led to a complication of mammoth enormity known as multi-drug resistance [4,146,147]. Owing to selection pressure, bacteria have generated resistance to these antibiotics by exploiting their inherent abilitiesmechanisms of efflux pumps, drug modulating enzymes and drug degrading enzymes.…”

Microbes, Antimicrobials and Resistance: The Battle Goes On

“…Will bacteria develop resistance to QSIs? [7]. Are we prepared to mutely witness yet another Never Ending battle?…”