Fructose furoic acid ester: An effective quorum sensing inhibitor against uropathogenic Escherichia coli.

ABSTRACT

Uropathogenic Escherichia coli (UPEC) are the most common cause of UTI, accounting for more than 90% infections in the normal and unobstructed urinary tracts. Multi-drug resistance (MDR) is an emerging threat to the mankind and hence, there is an urge to develop alternative therapies. Targeting quorum sensing (QS), a cell-cell communication process regulates various biofilm and virulence factors would be a most promising alternate which curbs the pathogenesis without killing the bacteria, unlike antibiotics. SdiA, a quorum regulator is well-known to control the behavioural changes of UPEC in establishing biofilm and virulence. Therefore, we have hypothesized that the SdiA-selective inhibitors derived from the plant, Melia dubia using the molecular docking would be a remarkable therapeutic candidate to down regulate the UPEC biofilm and virulence phenotypes. In this study, we have designed, synthesized and characterized the fructose-furoic acid ester by NMR and ESI-MS. In vitro studies revealed that the QSI-MD selectively inhibits UPEC adherence and confocal laser scanning microscopy (CLSM) analysis showed the effectiveness of QSI-MD to inhibit the UPEC biofilm. Genetic studies using qRT-PCR revealed the down-regulation of quorum sensing regulated genes (fimA, csgA, espA). Based on the findings, we could propose that the QSI-MD could possibly act through SdiA and show target-specific inhibition of biofilm and virulence. It is notable that more than 70 bacterial species execute their communication through the SdiA homologues (LuxIR system). Hence, the QSI-MD could be further developed as a broad-spectrum anti-infective drug.