Details

Autor(en) / Beteiligte

• Saini, Varsha
• Mehta, Devashish
• Gupta, Siddhi
• Kumar, Sandeep
• Rani, Parul
• Rana, Kajal
• Rajput, Kajal
• Jain, Dolly
• Pal, Garima
• Aggarwal, Bharti
• Pal, Sanjay
• Gupta, Sonu K.
• Kumar, Yashwant
• Ramu, Vemanna S.
• Bajaj, Avinash

Titel

Targeting Vancomycin-Resistant Enterococci (VRE) Infections and Van Operon-Mediated Drug Resistance Using Dimeric Cholic Acid–Peptide Conjugates

Ist Teil von

• Journal of medicinal chemistry, 2022-11, Vol.65 (22), p.15312-15326

Ort / Verlag

United States: American Chemical Society

Erscheinungsjahr

2022

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Emergence of vancomycin resistance in Gram-positive bacteria and the prevalence of vancomycin-resistant Enterococci (VRE) infections are highly alarming as very limited antibiotic options are available against VRE infections. Here, we present the synthesis of cholic acid-derived dimeric amphiphiles where two cholic acid moieties are tethered through carboxyl terminals using different alkylene spacers. Our investigations revealed that dimer 5 possessing a propylene spacer and glycine-valine peptides tethered on hydroxyl groups is the most effective antimicrobial against VRE. Dimer 5 can permeabilize bacterial membranes, generate reactive oxygen species, and clear preformed biofilms. We further demonstrate that dimer 5 downregulates vancomycin-mediated transcriptional activation of the vanHAX gene cluster and does not allow VSE to develop vancomycin resistance until 100 generations. Therefore, this study, for the first time, presents a bacterial membrane-targeting amphiphile that can mitigate VRE infections and inhibit the emergence of vancomycin resistance.