{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T21:37:22Z","timestamp":1790285842835,"version":"4.1.0"},"reference-count":50,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T00:00:00Z","timestamp":1741219200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Environmental Futures Research Institute, Griffith University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Phyllanthus emblica Linn. (commonly known as Amla or Indian Gooseberry) is commonly used in Ayurvedic medicine to treat respiratory infections, skin disorders, and gastrointestinal issues. The fruit contains an abundance of polyphenols, which contribute to its strong antioxidant properties. The antibacterial activity of fruit extracts derived from P. emblica against Escherichia coli, Staphylococcus aureus, and Klebsiella pneumoniae was determined along with the antibiotic-resistant variants extended-spectrum \u03b2-lactamase (ESBL) E. coli, methicillin-resistant S. aureus (MRSA), and ESBL K. pneumoniae. Disc diffusion and broth dilution assays were conducted to assess the activity of aqueous, methanolic, and ethyl acetate extracts, with large zones of inhibition of up to 15 mm on agar observed for S. aureus and MRSA. Minimum inhibitory concentration (MIC) values ranging from 158 to 1725 \u00b5g\/mL were calculated. The aqueous and methanolic extracts of P. emblica were less active against E. coli, ESBL E. coli, K. pneumoniae, and ESBL K. pneumoniae, with the only noteworthy MIC (633 \u00b5g\/mL) observed for the aqueous extract against K. pneumoniae. Interestingly, a lack of inhibition was observed on agar for any of the extracts against these bacteria. Liquid chromatography\u2013mass spectrometry (LC-MS) analysis identified several notable flavonoids, phenolic acids, terpenoids, and tannins. Notably, Artemia nauplii bioassays indicated that all extracts were nontoxic. The antibacterial activity and absence of toxicity in P. emblica extracts suggest their potential as candidates for antibiotic development, highlighting the need for further mechanistic and phytochemical investigations.<\/jats:p>","DOI":"10.3390\/microorganisms13030611","type":"journal-article","created":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T07:05:46Z","timestamp":1741331146000},"page":"611","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Phyllanthus emblica: Phytochemistry, Antimicrobial Potential with Antibiotic Enhancement, and Toxicity Insights"],"prefix":"10.3390","volume":"13","author":[{"given":"Gagan","family":"Tiwana","sequence":"first","affiliation":[{"name":"School of Pharmacy and Medical Sciences, Gold Coast Campus, Griffith University, Gold Coast 4222, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8732-8513","authenticated-orcid":false,"given":"Ian Edwin","family":"Cock","sequence":"additional","affiliation":[{"name":"School of Environment and Science, Nathan Campus, Griffith University, Brisbane 4111, Australia"},{"name":"Centre for Planetary Health and Food Security, Nathan Campus, Griffith University, 170 Kessels Rd., Nathan 4111, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2306-0829","authenticated-orcid":false,"given":"Matthew James","family":"Cheesman","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Medical Sciences, Gold Coast Campus, Griffith University, Gold Coast 4222, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,6]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2024, January 31). Antimicrobial Resistance. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/antimicrobial-resistance."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/S0140-6736(21)02724-0","article-title":"Global burden of bacterial antimicrobial resistance in 2019: A systematic analysis","volume":"399","author":"Murray","year":"2022","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1038\/s41570-021-00313-1","article-title":"Towards the Sustainable Discovery and Development of New Antibiotics","volume":"5","author":"Miethke","year":"2021","journal-title":"Nat. Rev. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.jaim.2017.05.004","article-title":"Development of botanicals to combat antibiotic resistance","volume":"8","author":"Gupta","year":"2017","journal-title":"J. Ayurveda Integr. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"152","DOI":"10.5530\/pc.2023.4.25","article-title":"A review of ayurvedic principles and the use of ayurvedic plants to control diarrhoea and gastrointestinal infections","volume":"13","author":"Tiwana","year":"2023","journal-title":"Pharmacogn. Commun."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.hermed.2016.03.001","article-title":"Antimicrobial resistance and synergy in herbal medicine","volume":"6","author":"Mundy","year":"2016","journal-title":"J. Herb. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1590\/S0102-695X2011005000014","article-title":"Modulation of drug resistance in Staphylococcus aureus by extract of mango (Mangifera indica L., anacardiaceae) peel","volume":"21","author":"Costa","year":"2011","journal-title":"Rev. Bras. Farmacogn."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1007\/s11130-024-01206-6","article-title":"Fruit extract and phenolic compounds of Phyllanthus emblica fruits as bioactivity enhancer of chloramphenicol against bacterial species","volume":"79","author":"Saini","year":"2024","journal-title":"Plant Foods Hum. Nutr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1007\/s00210-023-02624-0","article-title":"Synergistic antibacterial activity of Phyllanthus emblica fruits and its phytocompounds with ampicillin: A computational and experimental study","volume":"397","author":"Saini","year":"2023","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Summer, K., Browne, J., Hollanders, M., and Benkendorff, K. (2022). Out of control: The need for standardised solvent approaches and data reporting in antibiofilm assays incorporating dimethyl-sulfoxide (DMSO). Biofilm, 4.","DOI":"10.1016\/j.bioflm.2022.100081"},{"key":"ref_11","first-page":"142","article-title":"Assessment of the antimicrobial activity of the ethanolic extract of Phyllanthus emblica in combination with different classes of antibiotics against single and multi-drug resistant strains","volume":"4","author":"Jahan","year":"2015","journal-title":"J. Pharmacogn. Phytochem."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Tiwana, G., Cock, I.E., and Cheesman, M.J. (2024). Phyllanthus niruri Linn.: Antibacterial activity, phytochemistry, and enhanced antibiotic combinatorial strategies. Antibiotics, 13.","DOI":"10.3390\/antibiotics13070654"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Vitko, N.P., and Richardson, A.R. (2013). Laboratory maintenance of methicillin-resistant Staphylococcus aureus (MRSA). Curr. Protoc. Microbiol., 28.","DOI":"10.1002\/9780471729259.mc09c02s28"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Eloff, J.N. (2019). Avoiding pitfalls in determining antimicrobial activity of plant extracts and publishing the results. BMC Complement. Altern. Med., 19.","DOI":"10.1186\/s12906-019-2519-3"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4124","DOI":"10.1128\/JCM.01121-14","article-title":"When does 2 plus 2 equal 5? A review of antimicrobial synergy testing","volume":"52","author":"Doern","year":"2014","journal-title":"J. Clin. Microbiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1080\/15287390903232459","article-title":"Protective efficacy of the antioxidants vitamin E and Trolox against Microcystis aeruginosa and Microcystin-LR in Artemia franciscana Nauplii","volume":"72","author":"Ruebhart","year":"2009","journal-title":"J. Toxicol. Environ. Health A"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Cajka, T., Hricko, J., Rudl Kulhava, L., Paucova, M., Novakova, M., and Kuda, O. (2023). Optimization of mobile phase modifiers for fast LC-MS-based untargeted metabolomics and lipidomics. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24031987"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Angelini, P. (2024). Plant-derived antimicrobials and their crucial role in combating antimicrobial resistance. Antibiotics, 13.","DOI":"10.3390\/antibiotics13080746"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"112937","DOI":"10.1016\/j.jep.2020.112937","article-title":"Use of specific combinations of the triphala plant component extracts to potentiate the inhibition of gastrointestinal bacterial growth","volume":"260","author":"Tiwana","year":"2020","journal-title":"J. Ethnopharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Altemimi, A., Lakhssassi, N., Baharlouei, A., Watson, D.G., and Lightfoot, D.A. (2017). Phytochemicals: Extraction, isolation, and identification of bioactive compounds from plant extracts. Plants, 6.","DOI":"10.3390\/plants6040042"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1093\/jac\/dkn090","article-title":"Principles of assessing bacterial susceptibility to antibiotics using the agar diffusion method","volume":"61","author":"Bonev","year":"2008","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"875","DOI":"10.3109\/03639045.2014.971027","article-title":"Solubility and dissolution enhancement strategies: Current understanding and recent trends","volume":"41","author":"Jain","year":"2015","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1007\/s12088-017-0683-z","article-title":"The relationship between agar thickness and antimicrobial susceptibility testing","volume":"57","author":"Flanagan","year":"2017","journal-title":"Indian J. Microbiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0924-8579(00)00299-5","article-title":"Antibiotic resistance in staphylococci","volume":"16","author":"Livermore","year":"2000","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Kim, C., Mwangi, M., Chung, M., Milheirco, C., De Lencastre, H., and Tomasz, A. (2013). The mechanism of heterogeneous beta-lactam resistance in MRSA: Key role of the stringent stress response. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0082814"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Vaou, N., Stavropoulou, E., Voidarou, C., Tsigalou, C., and Bezirtzoglou, E. (2021). Towards advances in medicinal plant antimicrobial activity: A review study on challenges and future perspectives. Microorganisms, 9.","DOI":"10.3390\/microorganisms9102041"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"57","DOI":"10.4103\/phrev.phrev_21_17","article-title":"Developing new antimicrobial therapies: Are synergistic combinations of plant extracts\/compounds with conventional antibiotics the solution?","volume":"11","author":"Cheesman","year":"2017","journal-title":"Pharmacogn. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.cmi.2019.11.028","article-title":"Oral amoxicillin and amoxicillin\u2013clavulanic acid: Properties, indications and usage","volume":"26","author":"Huttner","year":"2020","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Khameneh, B., Eskin, N.A.M., Iranshahy, M., and Fazly Bazzaz, B.S. (2021). Phytochemicals: A promising weapon in the arsenal against antibiotic-resistant bacteria. Antibiotics, 10.","DOI":"10.3390\/antibiotics10091044"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"129","DOI":"10.4103\/ijmr.IJMR_2079_17","article-title":"Efflux pump inhibitors for bacterial pathogens: From bench to bedside","volume":"149","author":"Sharma","year":"2019","journal-title":"Indian J. Med. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5654","DOI":"10.1039\/D1CC01838H","article-title":"The antibacterial activity of peptide dendrimers and polymyxin B increases sharply above pH 7.4","volume":"57","author":"Cai","year":"2021","journal-title":"Chem. Commun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1093\/jac\/dkm357","article-title":"Polymyxin B for the treatment of multidrug-resistant pathogens: A critical review","volume":"60","author":"Zavascki","year":"2007","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_33","first-page":"1","article-title":"Phytochemistry, pharmacology and medicinal properties of Phyllanthus emblica Linn","volume":"20","author":"Gaire","year":"2014","journal-title":"Chin. J. Integr. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1080\/14786410601124664","article-title":"Studies on the chemical constituents of Phyllanthus emblica","volume":"21","author":"Yasin","year":"2007","journal-title":"Nat. Prod. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"100163","DOI":"10.1016\/j.prmcm.2022.100163","article-title":"Pharmacological properties of chebulinic acid and related ellagitannins from nature: An emerging contemporary bioactive entity","volume":"5","author":"Dhingra","year":"2022","journal-title":"Pharmacol. Res. Mod. Chin. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1021\/acs.jnatprod.9b00877","article-title":"Isolation, absolute configuration, and biological activities of chebulic acid and brevifolincarboxylic acid derivatives from Euphorbia hirta","volume":"83","author":"Yang","year":"2020","journal-title":"J. Nat. Prod."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"295","DOI":"10.31195\/ejejfs.787021","article-title":"Antimicrobial activity of citric acid against Escherichia coli, Staphylococcus aureus and Candida albicans as a sanitizer agent","volume":"8","author":"Eliuz","year":"2020","journal-title":"Eurasian J. For. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Adamczak, A., O\u017carowski, M., and Karpi\u0144ski, T.M. (2020). Antibacterial activity of some flavonoids and organic acids widely distributed in plants. J. Clin. Med., 9.","DOI":"10.3390\/jcm9010109"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1111\/lam.13420","article-title":"Impact of pH on citric acid antimicrobial activity against Gram-negative bacteria","volume":"72","author":"Burel","year":"2021","journal-title":"Lett. Appl. Microbiol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Li, X.-S., Xue, J.-Z., Qi, Y., Muhammad, I., Wang, H., Li, X.-Y., Luo, Y.-J., Zhu, D.-M., Gao, Y.-H., and Kong, L.-C. (2023). Citric acid confers broad antibiotic tolerance through alteration of bacterial metabolism and oxidative stress. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24109089"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.sajb.2020.12.028","article-title":"Phyllanthus emblica: A comprehensive review of its therapeutic benefits","volume":"138","author":"Ahmad","year":"2021","journal-title":"S. Afr. J. Bot."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1021\/jf404703k","article-title":"Composition and biological activities of hydrolyzable tannins of fruits of Phyllanthus emblica","volume":"62","author":"Yang","year":"2014","journal-title":"J. Agric. Food Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1080\/14786419.2014.895729","article-title":"Efflux-pump inhibitory activity of a gallotannin from Terminalia chebula fruit against multidrug-resistant uropathogenic Escherichia coli","volume":"28","author":"Bag","year":"2014","journal-title":"Nat. Prod. Res."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Bag, A., and Chattopadhyay, R.R. (2017). Synergistic antibiofilm efficacy of a gallotannin 1,2,6-tri-O-galloyl-\u03b2-D-glucopyranose from Terminalia chebula fruit in combination with gentamicin and trimethoprim against multidrug-resistant uropathogenic Escherichia coli biofilms. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0178712"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.micpath.2016.08.004","article-title":"Antimicrobial and enhancement of the antibiotic activity by phenolic compounds: Gallic acid, caffeic acid and pyrogallol","volume":"99","author":"Lima","year":"2016","journal-title":"Microb. Pathog."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Anek, P., Kumpangcum, S., Roytrakul, S., Khanongnuch, C., Saenjum, C., and Phannachet, K. (2024). Antibacterial activities of phenolic compounds in Miang extract: Growth inhibition and change in protein expression of extensively drug-resistant Klebsiella pneumoniae. Antibiotics, 13.","DOI":"10.3390\/antibiotics13060536"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1007\/s13659-020-00280-y","article-title":"Reversal of tetracycline resistance by cepharanthine, cinchonidine, ellagic acid and propyl gallate in a multidrug-resistant Escherichia coli","volume":"11","author":"Jenic","year":"2021","journal-title":"Nat. Prod. Bioprospect."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Zhou, H., Xu, M., Guo, W., Yao, Z., Du, X., Chen, L., Sun, Y., Shi, S., Cao, J., and Zhou, T. (2022). The antibacterial activity of kaempferol combined with colistin against colistin-resistant Gram-negative bacteria. Microbiol. Spectr., 10.","DOI":"10.1128\/spectrum.02265-22"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Jaisinghani, R.N. (2017). Antibacterial properties of quercetin. Microbiol. Res., 8.","DOI":"10.4081\/mr.2017.6877"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"34","DOI":"10.15586\/ijfs.v34i2.2196","article-title":"Antimicrobial synergistic effects of dietary flavonoids rutin and quercetin in combination with antibiotics gentamicin and ceftriaxone against E. coli (MDR) and P. mirabilis (XDR) strains isolated from human infections: Implications for food\u2013medicine interactions","volume":"34","author":"Alnour","year":"2022","journal-title":"Ital. J. Food Sci."}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/13\/3\/611\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:48:36Z","timestamp":1760028516000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/13\/3\/611"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,6]]},"references-count":50,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["microorganisms13030611"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms13030611","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,6]]}}}