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

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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 -B 1,4 -glucopyranose (Jatrophenin-1) and 1- O -galloyl-3,6-( R )-valoneoyl- D -B 1,4 -glucopyranose (Jatrophenin-2), together with vicenin-2, acacetin 7- O - β - D -glucopyranoside, ( E )- p -coumaric acid, and sucrose, based on the chromatographic characters, 1 H-, and 13 C 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.

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