TY  - JOUR
N1  - The copyright of this article belongs to ASM
ID  - open3167
UR  - https://journals.asm.org/doi/10.1128/spectrum.04876-22
IS  - 5
A1  - Chandal, Nishtha
A1  - Tambat, Rushikesh
A1  - Kalia, Ritu
A1  - Kumar, Gautam
A1  - Mahey, Nisha
A1  - Jachak , Sanjay
A1  - Nandanwar, Hemraj
Y1  - 2023/09/27/
N2  - NorA, an extensively studied efflux pump in Staphylococcus aureus, has been connected to fluoroquinolone, antiseptic, and disinfection resistance. Several studies have also emphasized how efflux pumps, including NorA, function as the first line of defense of S. aureus against antibiotics. In this study, we have screened some chemically synthesized indole derivatives for their activity as efflux pump inhibitors (EPIs). The derivative SMJ-5 was found to be a potent NorA efflux pump inhibitor among the screened indole derivatives, owing to increased ethidium bromide and norfloxacin accumulation in norA over-expressing S. aureus. The combination of SMJ-5 and ciprofloxacin demonstrated the eradication of S. aureus biofilm and prolonged the post-antibiotic effect more than ciprofloxacin alone. SMJ-5 was able to inhibit staphyloxanthin virulence. In in vitro time-kill trials and in vivo efficacy investigations, the combination enhanced the bactericidal activity of ciprofloxacin against S. aureus. Additionally, reverse transcription PCR results revealed that SMJ-5 also inhibits the NorA efflux pump indirectly at the transcriptional level.

PB  - ASM
JF  - Microbiology Spectrum  
VL  - 11
KW  - Staphylococcus aureus; efflux pump inhibitors (EPIs); major facilitator superfamily (MFS); multidrug resistance (MDR); norA efflux pump
TI  - Efflux pump inhibitory potential of indole derivatives as an arsenal against norA over-expressing Staphylococcus aureus
ER  -