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A synergy interaction of artocarpin and tetracycline against Pseudomonas aeruginosa and its mechanism of action on membrane permeability

  • Abdi Wira Septama EMAIL logo , Eldiza Puji Rahmi , Lucia Dwi Antika , Rizna Triana Dewi and Amit Jaisi
Published/Copyright: June 9, 2021
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Abstract

The emergence of antibacterial resistance has significantly increased. Pseudomonas aeruginosa is associated with nosocomial infection and difficult to control. Artocarpin, a flavonoid from Artocarpus heterophyllus Lam. exhibits several pharmacological properties including antibacterial. The study was performed to evaluate interaction between artocarpin and antibiotics including tetracycline against P. aeruginosa. Its mechanism of action on membrane permeability was also investigated. Broth microdilution was conducted for the susceptibility assay. The interaction of artocarpin and antibiotics was evaluated using checkerboard method, the effect on alteration of membrane cell was investigated using bacteriolysis and the released of 260 nm materials. Artocarpin showed moderate to weak activity against the Gram-negative bacteria including P. aeruginosa with MIC values in the range of 31.25–250 μg/mL. A synergistic effect against P. aeruginosa was produced by the combination of artocarpin (31.25 μg/mL) and tetracycline (1.95 μg/mL) with FICI of 0.37. The time-killing assay showed that artocarpin enhance the antibacterial activity of tetracycline against P. aeruginosa by completely inhibiting the bacterial growth. Additionally, the mixture of artocarpin (31.25 μg/mL) and tetracycline (1.95 μg/mL) disrupted membrane permeability and lead to cell death. These results proposed that the combination of artocarpin and tetracycline may be used to overcome P. aeruginosa infection.


Corresponding author: Abdi Wira Septama, Research Center for Chemistry, Indonesian Institute of Sciences, Kawasan PUSPIPTEK Serpong, Tangerang Selatan, Banten, 15314, Indonesia, E-mail:

Funding source: Southeast Asia-Europe Joint Funding Scheme

Award Identifier / Grant number: 2020

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: The authors wish to thank Southeast Asia-Europe Joint Funding Scheme for supports.

  3. Conflict of interest statement: The authors declare no conflicts of interest regarding this article.

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Received: 2021-03-14
Accepted: 2021-05-21
Published Online: 2021-06-09
Published in Print: 2022-01-27

© 2021 Walter de Gruyter GmbH, Berlin/Boston

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