PUBLICATION
Human vaginal Lactobacillus Jensenii -derived (-)-Terpinen-4-ol restores antibiotic sensitivity by inhibiting efflux pumps in drug resistant E. coli and K. pneumoniae
- Authors
- Nair, V.G., Unnikrishnan, V.K., Muralidharan, N., Venkatathri, B.N.S., Lowrence, R.C., Ybrd, R., Narbhavi, D., A, A., N, P., Nagarajan, S.
- ID
- ZDB-PUB-250830-11
- Date
- 2025
- Source
- Scientific Reports 15: 31823 (Journal)
- Registered Authors
- Keywords
- E. coli and K. pneumoniae, (-)-Terpinen-4-ol, Antibiotic resistance, Cell free supernatant, Efflux pump inhibition, Human vaginal Lactobacillus
- MeSH Terms
-
- Animals
- Anti-Bacterial Agents*/pharmacology
- Drug Resistance, Multiple, Bacterial/drug effects
- Erythromycin/pharmacology
- Escherichia coli*/drug effects
- Escherichia coli*/metabolism
- Female
- Humans
- Klebsiella pneumoniae*/drug effects
- Klebsiella pneumoniae*/metabolism
- Lactobacillus*/chemistry
- Lactobacillus*/metabolism
- Microbial Sensitivity Tests
- Probiotics/pharmacology
- Vagina*/microbiology
- Zebrafish
- PubMed
- 40883487 Full text @ Sci. Rep.
Citation
Nair, V.G., Unnikrishnan, V.K., Muralidharan, N., Venkatathri, B.N.S., Lowrence, R.C., Ybrd, R., Narbhavi, D., A, A., N, P., Nagarajan, S. (2025) Human vaginal Lactobacillus Jensenii -derived (-)-Terpinen-4-ol restores antibiotic sensitivity by inhibiting efflux pumps in drug resistant E. coli and K. pneumoniae. Scientific Reports. 15:31823.
Abstract
Probiotics present a promising preventive strategy for addressing urinary tract infections (UTIs) and serve as a viable alternative to conventional antimicrobial treatments. The integration of Lactobacillus-derived efflux pump inhibitors (EPIs) with conventional antibiotics presents a promising strategy to enhance the efficacy of treatments against antibiotic-resistant superbugs. In this study, we isolated eight vaginal Lactobacillus spp. from 54 healthy Indian women to explore their probiotic properties, specifically the ability of cell-free supernatant (CFS) from Lactobacillus jensenii. to inhibit efflux in Multi Drug Resistant (MDR) E. coli and K. pneumoniae. From the CFS, we obtained seven fractions, among which compound 7 (C7) markedly reduced the MIC of erythromycin against the K. pneumoniae MTCC 432 strain by 32-fold from 64 to 2 µg and restored its sensitivity, indicating potent efflux inhibitory activity. Gas Chromatography-Mass Spectrometry (GC-MS) analysis identified one major compound from the C7 fraction as Cyclohexen-1-ol, 4-methyl-1-(1-methylethyl)-, (R)-, also known as (-)-Terpinen-4-ol. In vivo studies using zebrafish infected with clinical strain of K. pneumoniae 1845 followed by treatment with (-)-Terpinen-4-ol and erythromycin caused a significant 7-log reduction in bacterial bioburden. Additionally, time-kill assay demonstrated that the combination of erythromycin with (-)-Terpinen-4-ol caused a remarkable 7-log reduction in both K. pneumoniae, and E. coli cell counts. Furthermore, (-)-Terpinen-4-ol -erythromycin combination exhibited a six-log reduction in bacterial burden in infected T24 bladder cell lines and was found to be non-toxic. This study underscores the efflux inhibitory potential of (-)-Terpinen-4-ol extracted from the CFS of human vaginal probiotics, paving the way for future pharmacological research and therapeutic applications.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping