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Efflux pump inhibitory potential of indole derivatives as an arsenal against norA over-expressing Staphylococcus aureus

DIR@IMTECH: CSIR-Institute of Microbial Technology

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Title Efflux pump inhibitory potential of indole derivatives as an arsenal against norA over-expressing Staphylococcus aureus
 
Creator Chandal, Nishtha
Tambat, Rushikesh
Kalia, Ritu
Kumar, Gautam
Mahey, Nisha
Jachak , Sanjay
Nandanwar, Hemraj
 
Subject QR Microbiology
 
Description 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.
 
Publisher ASM
 
Date 2023-09-27
 
Type Article
PeerReviewed
 
Relation https://journals.asm.org/doi/10.1128/spectrum.04876-22
http://crdd.osdd.net/open/3167/
 
Identifier Chandal, Nishtha and Tambat, Rushikesh and Kalia, Ritu and Kumar, Gautam and Mahey, Nisha and Jachak , Sanjay and Nandanwar, Hemraj (2023) Efflux pump inhibitory potential of indole derivatives as an arsenal against norA over-expressing Staphylococcus aureus. Microbiology Spectrum , 11 (5).