The rapid acquisition of multidrug-resistant (MDR) phenotypes by bacteria creates life-threatening complications in infection control. Accordingly, this study aims to investigate the antibacterial activity of the methanol extract of Talinum fruticosum leaves and its interaction effects with antibiotics against MDR Gram-negative bacteria. The broth microdilution method was used to evaluate the antibacterial activity and antibiotic-resistance modulation effects of the extract. The interaction between antibiotics and T. fruticosum leaf extract (TFLE) was conducted using the checkerboard assay. Phytochemical screening was assessed using standardized qualitative tests. TFLE displayed low antibacterial activity, with MICs ranging from 512 to 2048 µg/mL against the tested bacteria. Interestingly, TFLE at its subinhibitory concentration (MIC/8) enhanced the efficacy of antibiotics by 2-to 64-fold, particularly tetracycline, doxycycline, imipenem, kanamycin, and ciprofloxacin, against at least one of the examined MDR bacteria. In addition, TFLE displayed a synergistic effect (ƩFIC < 0.5) with kanamycin and doxycycline against K. pneumoniae K2 and E. aerogenes EA298. The phytochemical screening indicated that TFLE contained flavonoids, saponins, tannins, terpenoids, phenols, and anthocyanins. Overall, this study shows that T. fruticosum leaf extract could be used in combination with commonly used antibiotics to fight infections involving MDR bacteria. Therefore, further studies are needed to identify in this plant a likely nontoxic antibiotic modulator.
| Published in | Journal of Diseases and Medicinal Plants (Volume 12, Issue 1) |
| DOI | 10.11648/j.jdmp.20261201.12 |
| Page(s) | 11-19 |
| Creative Commons |
This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited. |
| Copyright |
Copyright © The Author(s), 2026. Published by Science Publishing Group |
Talinum fruticosum, Gram-Negative Bacteria, Multidrug-Resistance, Antibacterial, Synergy
Phytochemical classes | T. fruticosum leaf extract |
|---|---|
Terpenoids | + |
Saponins | + |
Alkaloids | - |
Phenols | + |
Flavonoids | + |
Tannins | + |
Anthocyanins | + |
Bacteria | T. fruticusum | Chloramphenicol | ||
|---|---|---|---|---|
MIC | MBC | MIC | MBC | |
E. coli | ||||
ATCC 10536 | 1024 | 2048 | 4 | 16 |
AG100 | — | — | 8 | 16 |
AG102 | 512 | — | 64 | >256 |
K. pneumoniae | ||||
ATCC 11296 | — | — | 4 | 32 |
KP2 | 2048 | — | 16 | 256 |
KP55 | — | — | 64 | >256 |
E. aerogenes | ||||
EA3 | — | — | 64 | >256 |
EA27 | 2048 | — | 8 | 64 |
EA298 | — | — | 64 | 256 |
P. aeruginosa | ||||
ATCC 27853 | 2048 | — | 8 | 64 |
PA01 | — | — | 8 | 32 |
PA124 | — | — | 32 | >256 |
Antibiotic | TFLE | Tested MDR bacteria, MIC (µg /mL), and modulation factor (in brackets) | |||||||
|---|---|---|---|---|---|---|---|---|---|
E. coli | P. aeruginosa | K. pneumoniae | E. aerogenes | Modulation effect (%) | |||||
AG100 | AG102 | PA121 | PA124 | K2 | KP55 | EA298 | |||
Kanamycin | 0 | <2 | 128 | <2 | 8 | >256 | 4 | >256 | |
MIC/8 | <2 (na) | 2 (64) | <2 (na) | 2 (4) | 64 (>4) | 4 (1) | 32 (>4) | 57.14 | |
Ciprofloxacin | 0 | 16 | <0.25 | 0.5 | >32 | 2 | 0.25 | 2 | |
MIC/8 | 4 (4) | <0.25 (na) | 0.25 (2) | 16 (>2) | 2 (1) | 0.25 (1) | 0.25 (4) | 57.14 | |
Streptomycin | 0 | 32 | 4 | 128 | 32 | 4 | <2 | 16 | |
MIC/8 | 8 (4) | 4 (1) | 64 (2) | 16 (2) | 4 (1) | <2 (na) | 16 (1) | 42.86 | |
Tetracycline | 0 | 32 | 64 | 128 | 32 | 128 | 256 | 128 | |
MIC/8 | 8 (4) | 32 (2) | 64 (2) | 16 (2) | 64 (2) | 256 (1) | 16 (8) | 85.71 | |
Doxycyclin | 0 | 128 | 16 | 128 | 64 | 64 | 128 | 64 | |
MIC/8 | 64 (2) | 4 (4) | 128 (1) | 2 (32) | 8 (8) | 128 (1) | 4 (8) | 71.43 | |
Ampicillin | 0 | >256 | >256 | >256 | 256 | >256 | >256 | >256 | |
MIC/8 | 128 (>2) | 128 (>2) | 256 (>1) | 16 (16) | >256 (na) | >256 (na) | >256 (na) | 42.86 | |
Ceftriaxone | 0 | 8 | 64 | 64 | 64 | 128 | 64 | 64 | |
MIC/8 | 4 (2) | 64 (1) | 64 (1) | 32 (2) | 32 (4) | 256 (0.25) | 64 (1) | 42.86 | |
Imipenem | 0 | 64 | 64 | 32 | 32 | 32 | 64 | 32 | |
MIC/8 | 16 (4) | 32 (2) | 128 (0.25) | 8 (4) | 16 (2) | 32 (2) | 64 (0.5) | 71.43 | |
Vancomycin | 0 | 64 | >256 | >256 | 256 | >256 | 128 | >256 | |
MIC/8 | 8 (8) | >256 (na) | >256 (na) | 128 (2) | 256 (>1) | 64 (2) | 256 (>1) | 42.86 | |
Antibiotic | Bacteria | Fractional inhibitory concentration | ƩFIC | Interpretation | |
|---|---|---|---|---|---|
Antibiotic | Extract | ||||
Kanamycin | K. pneumoniae K2 | 0.25 | 0.125 | 0.32 | Synergy |
E. aerogenes EA298 | 0.25 | 0.06 | 0.31 | Synergy | |
E. coli AG102 | 0.5 | 0.03 | 0.53 | Additivity | |
Doxycyclin | K. pneumoniae K2 | 0, 03 | 0.25 | 0.28 | Synergy |
E. aerogenes EA298 | 0.01 | 0.12 | 0.13 | Synergy | |
E. coli AG102 | 0.03 | 0.5 | 0.53 | Additivity | |
AMR | Antimicrobial Resistance |
DMSO | Dimethyl Sulfoxide |
FIC | Fractional Inhibitory Concentration |
INT | p-Iodonitrotetrazolium Chloride |
MBC | Minimum Bactericidal Concentration |
MDR | Multidrug-Resistant |
MF | Modulation Factor |
MHB | Mueller-Hinton Broth |
MIC | Minimum Inhibitory Concentration |
RND | Resistance Nodulation Cell Division |
TFLE | Talinum fruticosum Leaf Extract |
| [1] | Sulis G, Sayood S, Gandra S. Antimicrobial resistance in low- and middle-income countries: current status and future directions. Expert Rev Anti Infect Ther. 2022; 20(2): 147-60. |
| [2] | Wright GD. Molecular mechanisms of antibiotic resistance. Chem Commun (Camb). 2011; 47(14): 4055-61. |
| [3] | Blair JM, Webber MA, Baylay AJ, Ogbolu DO, Piddock LJ. Molecular mechanisms of antibiotic resistance. Nat Rev Microbiol. 2015; 13(1): 42-51. |
| [4] |
O’Neill J. Review on Antimicrobial Resistance. Tackling drug resistant infections globally: final report and recommendations. UK: HM Government and Welcome Trust. 2016.
https://amr-review.org/sites/default/files/160518_Final%20paper_with%20cover.pdf |
| [5] | Rossolini GM, Arena F, Pecile P, Pollini S. Update on the antibiotic resistance crisis. Curr Opin Pharmacol. 2014; 18: 56-60. |
| [6] | Golkar Z, Bagasra O, Pace DG. Bacteriophage therapy: a potential solution for the antibiotic resistance crisis. J Infect Dev Ctries 2014; 8(2): 129-36. |
| [7] | Li XZ, Poole K, Nikaido H. Contributions of MexAB-OprM and an EmrE homolog to intrinsic resistance of Pseudomonas aeruginosa to aminoglycosides and dyes. Antimicrob Agents Chemother. 2003; 47(1): 27-33. |
| [8] | Kuete V, Ngameni B, Tangmouo JG, Bolla JM, Alibert-Franco S, Ngadjui BT, Pagès JM. Efflux pumps are involved in the defense of Gram-negative bacteria against the natural products isobavachalcone and diospyrone. Antimicrob Agents Chemother. 2010; 54(5): 1749-52. |
| [9] | Kim HS. Do not put too much value on conventional medicines. J Ethnopharmacol. 2005; 100(1-2): 37-9. |
| [10] | Rossiter SE, Fletcher MH, Wuest WM. Natural Products as Platforms To Overcome Antibiotic Resistance. Chem Rev. 2017; 117(19): 12415-12474. |
| [11] | Porras G, Chassagne F, Lyles JT, Marquez L, Dettweiler M, Salam AM, Samarakoon T, Shabih S, Farrokhi DR, Quave CL. Ethnobotany and the Role of Plant Natural Products in Antibiotic Drug Discovery. Chem Rev. 2021; 121(6): 3495-3560. |
| [12] | Tyers M, Wright GD. Drug combinations: a strategy to extend the life of antibiotics in the 21st century. Nat Rev Microbiol. 2019; 17(3): 141-55. |
| [13] | Tankeo SB, Lacmata ST, Noumedem JA, Dzoyem JP, Kuiate JR, Kuete V. Antibacterial and antibiotic-potentiation activities of some Cameroonian food plants against multi-drug resistant gram-negative bacteria. Chin J Integr Med. 2014; 20(7): 546-54. |
| [14] | Fankam AG, Kuiate JR, Kuete V. Antibacterial and antibiotic resistance-modifying activity of the extracts from Allanblackia gabonensis, Combretum molle and Gladiolus quartinianus against Gram-negative bacteria, including multi-drug resistant phenotypes. BMC Complement Altern Med. 2015; 15: 206. |
| [15] | Ngakam R, Matieta VY, Kengne Fonkou G, Mapie Tiwa S, Megaptche JF, Nayim P, Mbaveng AT, Kuete V. Antibacterial potential and modes of action of methanol extracts of flowers and leaves of Vernonia glabra (Steetz) Vatke (Asteraceae) against multidrug-resistant Gram-negative bacteria overexpressing efflux pumps. Invest Med Chem Pharmacol. 2024; 7(1): 87. |
| [16] | Swarna J, Ravindhran R. Pharmacognostical and phytochemical evaluation of Talinum triangulare (Jacq.) Willd. Int J Pharm Pharm Sci. 2013; 5(2): 249-256. |
| [17] | Barman D, Puro KN, Boruah JL, Kumar D, Medhi K, Mazumder B, Baishya R. Talinum triangulare (Jacq.) Willd: A review of its traditional uses, phytochemistry, and pharmacology, along with network pharmacology analysis of its components and targets. Food Chem Adv. 2025; 5: 100768. |
| [18] | John NAA, Shobana G. Anti-inflammatory activity of Talinum fruticosum l. on formalin-induced paw edema in albino rats. J App Pharm Sci. 2012; 02(01): 123-7. |
| [19] | Oguntona T. Green Leafy Vegetables. In: Nutritional Quality of Plant Food, [Osagie, A. U. and O. U. Eka (Eds.)]. Ambik Press. 1998, p. 120-33. |
| [20] | Offiah NV, Makama S, Elisha IL, Makoshi MS, Gotep JG, Dawurung CJ, Oladipo OO, Lohlum AS, Shamaki D. Ethnobotanical survey of medicinal plants used in the treatment of animal diarrhoea in Plateau State, Nigeria. BMC Vet Res. 2011; 7: 36. |
| [21] | Bioltif YE. Review on the Medicinal Potentials of Waterleaf (Talinum triangulare). Mediterr J Basic appl Sci 2020; 4(2): 01-07. |
| [22] | Liang D, Zhou Q, Gong W, Wang Y, Nie Z, He H, Li J, Wu J, Wu C, Zhang J. Studies on the antioxidant and hepatoprotective activities of polysaccharides from Talinum triangulare. J Ethnopharmacol 2011; 136(2): 316-21. |
| [23] | Esho BA, Samuel B, Akinwunmi KF, Oluyemi WM. Membrane stabilization and inhibition of protein denaturation as mechanisms of the Anti-inflammatory activity of some plant species. Trends Pharmacol Sci 2021: 7(4): 269-278. |
| [24] | Oluba OM, Adebiyi FD, Dada AA, Ajayi AA, Adebisi KE, Josiah SJ, Odutuga AA. Effects of Talinum triangulare leaf flavonoid extract on streptozotocin-induced hyperglycemia and associated complications in rats. Food Sci Nutr. 2018 Oct 11; 7(2): 385-394. |
| [25] | Ebuehi, OA, Ajagun-Ogunleye MO. Neurochemical impact of the aqueous extract of Vernonia amygdalina and Talinum triangulare on learning and memory in male Wistar rats. Int J Brain Cogn Sci. 2017; 6(5): 81-8. |
| [26] | Ranjan A, Ramachandran S, Gupta N, Kaushik I, Wright S, Srivastava S, Das H, Srivastava S, Prasad S, Srivastava SK. Role of Phytochemicals in Cancer Prevention. Int J Mol Sci 2019; 20(20): 4981. |
| [27] | Ojo OA, Oyinloye BE, Ojo AB, Afolabi OB, Peters OA., Olaiya O. et al. Green synthesis of silver nanoparticles (AgNPs) using Talinum triangulare (Jacq.) Willd. Leaf extract and monitoring their antimicrobial activity. J Bionanosci. 2017; 11: 292-296. |
| [28] | Elemike EE, Onwudiwe DC, Fayemi OE, Ekennia AC, Ebenso EE, Tiedt LR. Biosynthesis, electrochemical, antimicrobial and antioxidant studies of silver nanoparticles mediated by Talinum triangulare aqueous leaf extract. J Clust Sci 2017; 28: 309-330. |
| [29] | Tiwari P, Kumar B, Kaur M, Kaur G, Kaur H. Phytochemical screening and extraction: a review. Int Pharm Sci. 2011; 1(1): 98-106. |
| [30] | Kuete V. Medicinal Plant Research in Africa: Pharmacology and Chemistry In: Pharmacology and Chemistry. Edited by Kuete V, 1 Ed. Oxford: Elsevier. 2013. |
| [31] | Voukeng IK, Kuete V, Dzoyem JP, Fankam AG, Noumedem JA, Kuiate JR, Pages JM. Antibacterial and antibiotic-potentiation activities of the methanol extract of some Cameroonian spices against Gram-negative multi-drug resistant phenotypes. BMC Res Notes. 2012; 5: 299. |
| [32] | Seukep JA, Sandjo LP, Ngadjui BT, Kuete V. Antibacterial and antibiotic-resistance modifying activity of the extracts and compounds from Nauclea pobeguinii against Gram-negative multi-drug resistant phenotypes. BMC Complement Altern Med. 2016; 16: 193. |
| [33] | Eloff JN. A sensitive and quick microplate method to determine the minimal inhibitory concentration of plant extracts for bacteria. Planta Med. 1998; 64(8): 711-713. |
| [34] | Kuete V, Ngameni B, Simo CC, Tankeu RK, Ngadjui BT, Meyer JJ, Lall N, Kuiate JR. Antimicrobial activity of the crude extracts and compounds from Ficus chlamydocarpa and Ficus cordata (Moraceae). J Ethnopharmacol. 2008; 120(1): 17-24. |
| [35] | Kuete V. Potential of African medicinal plants against Enterobacteria: Classification of plants antibacterial agents. In: African Flora to Fight Bacterial Resistance, Part I: Standards for the Activity of Plant-Derived Products. Ed; Kuete V. Advances in Botanical Research. 106(1): 151-335. |
| [36] | Tankeo SB, Kuete V. 2023. Chapter Seven - African plants acting on Pseudomonas aeruginosa: Cut-off points for the antipseudomonal agents from plants. Adv Bot Res 2023; 106: p.337-412. |
| [37] | Fankam AG, Kuiate JR, Kuete V. Antibacterial and antibiotic resistance modulatory activities of leaves and bark extracts of Recinodindron heudelotii (Euphorbiaceae) against multidrug-resistant Gram-negative bacteria. BMC Complement Altern Med. 2017; 17(1): 168. |
| [38] | Prasch S, Duran AG, Chinchilla N, Molinillo JM, Macías FA, Bucar F. Resistance modulatory and efflux-inhibitory activities of capsaicinoids and capsinoids. Bioorg Chem. 2019; 82: 378-84. |
| [39] | Daly SM, Sturge CR, Greenberg DE. Inhibition of Bacterial Growth by Peptide-Conjugated Morpholino Oligomers. In: Moulton, H., Moulton, J. (eds) Morpholino Oligomers. Methods in Molecular Biology, vol 1565. Humana Press, New York, NY, 2017. |
| [40] | European Committee for Antimicrobial Susceptibility Testing (EUCAST) of the European Society of Clinical Microbiology and Infectious Dieases (ESCMID). EUCAST Definitive Document E.Def 1.2, May 2000: Terminology relating to methods for the determination of susceptibility of bacteria to antimicrobial agents. Clin Microbiol Infect. 2000; 6(9): 503-8. |
| [41] | Venter H. Reversing resistance to counter antimicrobial resistance in the World Health Organisation's critical priority of most dangerous pathogens. Biosci Rep. 2019; 39(4): BSR20180474. |
| [42] | Khare T, Anand U, Dey A, Assaraf YG, Chen ZS, Liu Z, Kumar V. Exploring Phytochemicals for Combating Antibiotic Resistance in Microbial Pathogens. Front Pharmacol. 2021; 12: 720726. |
| [43] | Molyneux RJ, Lee ST, Gardner DR, Panter KE, James LF. Phytochemicals: the good, the bad and the ugly? Phytochemistry. 2007; 68(22-24): 2973-85. |
| [44] | Ikewuchi CC, Ikewuchi JC, Ifeanacho MO. Bioactive phytochemicals in an aqueous extract of the leaves of Talinum triangulare. Food Sci Nutr. 2016; 5(3): 696-701. |
| [45] | Vauzour D. Dietary polyphenols as modulators of brain functions: biological actions and molecular mechanisms underpinning their beneficial effects. Oxid Med Cell Longev. 2012; 2012: 914273. |
| [46] | González-Bello C. Antibiotic adjuvants - A strategy to unlock bacterial resistance to antibiotics. Bioorg Med Chem Lett. 2017; 27(18): 4221-4228. |
| [47] | Veras HN, Rodrigues FF, Colares AV, Menezes IR, Coutinho HD, Botelho MA, Costa JG. Synergistic antibiotic activity of volatile compounds from the essential oil of Lippia sidoides and thymol. Fitoterapia. 2012; 83(3): 508-12. |
| [48] | Waditzer M, Bucar F. Flavonoids as Inhibitors of Bacterial Efflux Pumps. Molecules. 2021; 26(22): 6904. |
| [49] | Sharma A, Biharee A, Kumar A, Jaitak V. Antimicrobial Terpenoids as a Potential Substitute in Overcoming Antimicrobial Resistance. Curr Drug Targets. 2020; 21(14): 1476-94. |
| [50] | Dias KJSO, Miranda GM, Bessa JR, Araújo ACJ, Freitas PR, Almeida RS, Paulo CLR, Neto JBA, Coutinho HDM, Ribeiro-Filho J. Terpenes as bacterial efflux pump inhibitors: A systematic review. Front Pharmacol. 2022; 13: 953982. |
| [51] | Suganya T, Packiavathy IASV, Aseervatham GSB, Carmona A, Rashmi V, Mariappan S, Devi NR, Ananth DA. Tackling Multiple-Drug-Resistant Bacteria with Conventional and Complex Phytochemicals. Front Cell Infect Microbiol. 2022; 12: 883839. |
APA Style
Fankam, A. G., Diffo, V. L., Mouozong, R., Matieta, V. Y., Megaptche, F. J., et al. (2026). Talinum fruticosum (L.) Juss. (Talinaceae), an Edible and Medicinal Plant, Enhances the Activity of Antibiotics Against Multidrug-Resistant Gram-Negative Bacteria. Journal of Diseases and Medicinal Plants, 12(1), 11-19. https://doi.org/10.11648/j.jdmp.20261201.12
ACS Style
Fankam, A. G.; Diffo, V. L.; Mouozong, R.; Matieta, V. Y.; Megaptche, F. J., et al. Talinum fruticosum (L.) Juss. (Talinaceae), an Edible and Medicinal Plant, Enhances the Activity of Antibiotics Against Multidrug-Resistant Gram-Negative Bacteria. J. Dis. Med. Plants 2026, 12(1), 11-19. doi: 10.11648/j.jdmp.20261201.12
AMA Style
Fankam AG, Diffo VL, Mouozong R, Matieta VY, Megaptche FJ, et al. Talinum fruticosum (L.) Juss. (Talinaceae), an Edible and Medicinal Plant, Enhances the Activity of Antibiotics Against Multidrug-Resistant Gram-Negative Bacteria. J Dis Med Plants. 2026;12(1):11-19. doi: 10.11648/j.jdmp.20261201.12
@article{10.11648/j.jdmp.20261201.12,
author = {Aimé Gabriel Fankam and Varelle Lambou Diffo and Richard Mouozong and Valaire Yemene Matieta and Fabrice Junior Megaptche and Victor Kuete},
title = {Talinum fruticosum (L.) Juss. (Talinaceae), an Edible and Medicinal Plant, Enhances the Activity of Antibiotics Against Multidrug-Resistant Gram-Negative Bacteria},
journal = {Journal of Diseases and Medicinal Plants},
volume = {12},
number = {1},
pages = {11-19},
doi = {10.11648/j.jdmp.20261201.12},
url = {https://doi.org/10.11648/j.jdmp.20261201.12},
eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.jdmp.20261201.12},
abstract = {The rapid acquisition of multidrug-resistant (MDR) phenotypes by bacteria creates life-threatening complications in infection control. Accordingly, this study aims to investigate the antibacterial activity of the methanol extract of Talinum fruticosum leaves and its interaction effects with antibiotics against MDR Gram-negative bacteria. The broth microdilution method was used to evaluate the antibacterial activity and antibiotic-resistance modulation effects of the extract. The interaction between antibiotics and T. fruticosum leaf extract (TFLE) was conducted using the checkerboard assay. Phytochemical screening was assessed using standardized qualitative tests. TFLE displayed low antibacterial activity, with MICs ranging from 512 to 2048 µg/mL against the tested bacteria. Interestingly, TFLE at its subinhibitory concentration (MIC/8) enhanced the efficacy of antibiotics by 2-to 64-fold, particularly tetracycline, doxycycline, imipenem, kanamycin, and ciprofloxacin, against at least one of the examined MDR bacteria. In addition, TFLE displayed a synergistic effect (ƩFIC K. pneumoniae K2 and E. aerogenes EA298. The phytochemical screening indicated that TFLE contained flavonoids, saponins, tannins, terpenoids, phenols, and anthocyanins. Overall, this study shows that T. fruticosum leaf extract could be used in combination with commonly used antibiotics to fight infections involving MDR bacteria. Therefore, further studies are needed to identify in this plant a likely nontoxic antibiotic modulator.},
year = {2026}
}
TY - JOUR T1 - Talinum fruticosum (L.) Juss. (Talinaceae), an Edible and Medicinal Plant, Enhances the Activity of Antibiotics Against Multidrug-Resistant Gram-Negative Bacteria AU - Aimé Gabriel Fankam AU - Varelle Lambou Diffo AU - Richard Mouozong AU - Valaire Yemene Matieta AU - Fabrice Junior Megaptche AU - Victor Kuete Y1 - 2026/02/25 PY - 2026 N1 - https://doi.org/10.11648/j.jdmp.20261201.12 DO - 10.11648/j.jdmp.20261201.12 T2 - Journal of Diseases and Medicinal Plants JF - Journal of Diseases and Medicinal Plants JO - Journal of Diseases and Medicinal Plants SP - 11 EP - 19 PB - Science Publishing Group SN - 2469-8210 UR - https://doi.org/10.11648/j.jdmp.20261201.12 AB - The rapid acquisition of multidrug-resistant (MDR) phenotypes by bacteria creates life-threatening complications in infection control. Accordingly, this study aims to investigate the antibacterial activity of the methanol extract of Talinum fruticosum leaves and its interaction effects with antibiotics against MDR Gram-negative bacteria. The broth microdilution method was used to evaluate the antibacterial activity and antibiotic-resistance modulation effects of the extract. The interaction between antibiotics and T. fruticosum leaf extract (TFLE) was conducted using the checkerboard assay. Phytochemical screening was assessed using standardized qualitative tests. TFLE displayed low antibacterial activity, with MICs ranging from 512 to 2048 µg/mL against the tested bacteria. Interestingly, TFLE at its subinhibitory concentration (MIC/8) enhanced the efficacy of antibiotics by 2-to 64-fold, particularly tetracycline, doxycycline, imipenem, kanamycin, and ciprofloxacin, against at least one of the examined MDR bacteria. In addition, TFLE displayed a synergistic effect (ƩFIC K. pneumoniae K2 and E. aerogenes EA298. The phytochemical screening indicated that TFLE contained flavonoids, saponins, tannins, terpenoids, phenols, and anthocyanins. Overall, this study shows that T. fruticosum leaf extract could be used in combination with commonly used antibiotics to fight infections involving MDR bacteria. Therefore, further studies are needed to identify in this plant a likely nontoxic antibiotic modulator. VL - 12 IS - 1 ER -