# The gene-modulating power of Tannins isolated from Jatropha integerrima flowers on the transcriptomic profile of multidrug-resistant Klebsiella pneumoniae

## TL;DR

This paper explores tannins from Jatropha integerrima flowers that can combat antibiotic-resistant Klebsiella pneumoniae by affecting its gene expression and biofilm formation.

## Contribution

The study identifies two novel tannins with antimicrobial and antibiofilm properties against multidrug-resistant Klebsiella pneumoniae.

## Key findings

- The tannins downregulated key biofilm-related genes in Klebsiella pneumoniae.
- The compounds showed strong binding to enzymes linked to antibiotic resistance.
- The tannins exhibited potent antimicrobial and antibiofilm activity in assays.

## Abstract

The continuous increase in antibiotic resistance necessitates a global need to search for new sustainable antimicrobial agents, such as plant-delivered antimicrobial components. This study investigates the antimicrobial and antibiofilm properties of two tannins isolated from the flowers of Jatropha integerrima against multidrug-resistant Klebsiella pneumoniae. The two active tannins were isolated from the methanol-soluble portion of 70% aqueous methanol flower extract, by consecutive column chromatography. Their antimicrobial activity against the resistant K. pneumoniae isolate (BKP-122) was assessed through agar well diffusion and minimum inhibitory concentration (MIC) assays. Their antibiofilm activity was evaluated by using the microtiter plate method and real-time PCR to reveal their effect on the biofilm-associated genes.

Their structures were identified as 2 hydrolysable ellagitannins, namely 1-O-galloyl-3,6-(R)-hexahydroxydiphenoyl-D-B1,4-glucopyranose (Jatrophenin-1) and 1-O-galloyl-3,6-(R)-valoneoyl-D-B1,4-glucopyranose (Jatrophenin-2), together with vicenin-2, acacetin 7-O-β-D-glucopyranoside, (E)-p-coumaric acid, and sucrose, based on the chromatographic characters, 1H-, and 13C NMR analyses. They were found to have potent antimicrobial activity and antibiofilm activity against the resistant K. pneumoniae isolate (BKP-122). Real-time PCR analysis indicated that treatment with tannins resulted in the downregulation of critical biofilm-related genes, including luxS, mrkA, pgaA, wzm, and wbbM. Additionally, the two compounds showed high docking binding scores against Topoisomerase IV, KPLpxH, and β-lactamase enzymes, and stable complexes, as evidenced by binding energy values ranging from -8.2 to -10 kcal/mol. These findings underscore the effectiveness of J. integerrima tannins as a viable therapeutic strategy to combat antibiotic resistance and biofilm-related infections, highlighting their role in modulating bacterial gene expression and biofilm development.

The online version contains supplementary material available at 10.1038/s41598-025-32490-0.