{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T10:31:54Z","timestamp":1781519514611,"version":"3.54.1"},"reference-count":45,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2019,5,13]],"date-time":"2019-05-13T00:00:00Z","timestamp":1557705600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>The natural population of the aquatic environment supports a diverse aquatic biota and a robust seafood industry. However, this environment also provides an appropriate niche for the growth of pathogenic bacteria that cause problems for human health. For example, species of the genus Vibrio inhabit marine and estuarine environments. This genus includes species that are pathogenic to aquaculture, invertebrates, and humans. In humans, they can cause prominent diseases like gastroenteritis, wound infections, and septicemia. The increased number of multidrug resistant (MDR) Vibrio strains has drawn the attention of the scientific community to develop new broad-spectrum antibiotics. Hence, in this paper we report the bactericidal effects of compounds derived from Piper betel plants: piperidine, chlorogenic acid, and eugenyl acetate, against various strains of Vibrio species. The different MIC90 values were approximately in a range of 2\u20136 mg\/mL, 5\u201316 mg\/mL, 5\u201320 mg\/mL, and 30\u201380 mg\/mL, for piperidine, chlorogenic acid, and eugenyl acetate, respectively. Piperidine showed the best anti-Vibrio effect against the five Vibrio species tested. Interestingly, combinations of sub-inhibitory concentrations of piperidine, chlorogenic acid, and eugenyl acetate showed inhibitory effects in the Vibrio strains. Furthermore, these compounds showed synergism or partial synergism effects against MDR strains of the Vibrio species when they were incubated with antibiotics (ampicillin and chloramphenicol).<\/jats:p>","DOI":"10.3390\/pathogens8020064","type":"journal-article","created":{"date-parts":[[2019,5,13]],"date-time":"2019-05-13T11:00:57Z","timestamp":1557745257000},"page":"64","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Piper betel Compounds Piperidine, Eugenyl Acetate, and Chlorogenic Acid Are Broad-Spectrum Anti-Vibrio Compounds that Are Also Effective on MDR Strains of the Pathogen"],"prefix":"10.3390","volume":"8","author":[{"given":"Erika","family":"Acosta-Smith","sequence":"first","affiliation":[{"name":"Programa Regional del Noroeste para el Doctorado en Biotecnolog\u00eda-FCQB, Universidad Aut\u00f3noma de Sinaloa, Avenida de las Am\u00e9ricas y Josefa Ortiz (Ciudad Universitaria), Culiac\u00e1n Sin. 80030, Mexico"},{"name":"CIASaP, Facultad de Medicina, Universidad Aut\u00f3noma de Sinaloa. Cedros y Sauces, Fracc. Fresnos, Culiac\u00e1n Sin. 80246, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nidia","family":"Leon-Sicairos","sequence":"additional","affiliation":[{"name":"CIASaP, Facultad de Medicina, Universidad Aut\u00f3noma de Sinaloa. Cedros y Sauces, Fracc. Fresnos, Culiac\u00e1n Sin. 80246, Mexico"},{"name":"Departamento de Investigaci\u00f3n, Hospital Pedi\u00e1trico de Sinaloa, Blvd. Constituci\u00f3n y Donato Guerra S\/N, Almada, Culiac\u00e1n Sin. 80200, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandeep","family":"Tiwari","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Gen\u00e9tica Celular e Molecular, Programa de P\u00f3s-gradua\u00e7\u00e3o em Bioinform\u00e1tica, Instituto de Ci\u00eancias Biol\u00f3gicas (ICB), Universidade Federal de Minas Gerais, Av. Antonio Carlos 6627, Pampulha, Belo Horizonte, CEP 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9734-8019","authenticated-orcid":false,"given":"Hector","family":"Flores-Villase\u00f1or","sequence":"additional","affiliation":[{"name":"CIASaP, Facultad de Medicina, Universidad Aut\u00f3noma de Sinaloa. Cedros y Sauces, Fracc. Fresnos, Culiac\u00e1n Sin. 80246, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Canizalez-Roman","sequence":"additional","affiliation":[{"name":"CIASaP, Facultad de Medicina, Universidad Aut\u00f3noma de Sinaloa. Cedros y Sauces, Fracc. Fresnos, Culiac\u00e1n Sin. 80246, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranjith","family":"Kumavath","sequence":"additional","affiliation":[{"name":"Department of Genomic Sciences, School of Biological Sciences, Central University of Kerala, Kasaragod 671121, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3880-5886","authenticated-orcid":false,"given":"Preetam","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Department of Computer Science, Virginia Commonwealth University, Richmond, VA 23284, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4775-2280","authenticated-orcid":false,"given":"Vasco","family":"Azevedo","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Gen\u00e9tica Celular e Molecular, Programa de P\u00f3s-gradua\u00e7\u00e3o em Bioinform\u00e1tica, Instituto de Ci\u00eancias Biol\u00f3gicas (ICB), Universidade Federal de Minas Gerais, Av. Antonio Carlos 6627, Pampulha, Belo Horizonte, CEP 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2557-7768","authenticated-orcid":false,"given":"Debmalya","family":"Barh","sequence":"additional","affiliation":[{"name":"Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology (IIOAB), Nonakuri, Purba Medinipur, West Bengal-721172, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,5,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.4315\/0362-028X.JFP-11-001","article-title":"Occurrence of vibrio spp. In fish and shellfish collected from the swiss market","volume":"74","author":"Scharer","year":"2011","journal-title":"J. Food Prot."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5107","DOI":"10.1128\/AEM.71.9.5107-5115.2005","article-title":"Phylogeny and molecular identification of vibrios on the basis of multilocus sequence analysis","volume":"71","author":"Thompson","year":"2005","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1128\/CMR.1.3.245","article-title":"Current perspectives on the epidemiology and pathogenesis of clinically significant vibrio spp.","volume":"1","author":"Janda","year":"1988","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_4","first-page":"275","article-title":"Additional serovars and inter-o antigenic relationships of vibrio cholerae","volume":"30","author":"Shimada","year":"1977","journal-title":"Jpn. J. Med. Sci. Boil."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1128\/MMBR.62.4.1301-1314.1998","article-title":"Epidemiology, genetics, and ecology of toxigenic vibrio cholerae","volume":"62","author":"Faruque","year":"1998","journal-title":"Microbiol. Mol. Boil. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1093\/clinids\/21.5.1330","article-title":"Primary septicemia caused by vibrio cholerae non-o1 acquired on cape cod, massachusetts","volume":"21","author":"Kontoyiannis","year":"1995","journal-title":"Clin. Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.diagmicrobio.2004.04.016","article-title":"Non-o1 vibrio cholerae septicemia: Case report, discussion of literature, and relevance to bioterrorism","volume":"49","author":"Anderson","year":"2004","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/S0140-6736(03)15328-7","article-title":"Cholera","volume":"363","author":"Sack","year":"2004","journal-title":"Lancet"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e384","DOI":"10.1016\/j.ijid.2009.06.020","article-title":"Epidemics of severe cholera caused by el tor vibrio cholerae o1 ogawa possessing the ctxb gene of the classical biotype in Orissa, India","volume":"14","author":"Pal","year":"2010","journal-title":"Int. J. Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"987","DOI":"10.3201\/eid1406.080129","article-title":"Vibrio cholerae o1 hybrid el tor strains, asia and africa","volume":"14","author":"Safa","year":"2008","journal-title":"Emerg. Infect. Dis."},{"key":"ref_11","first-page":"171","article-title":"Vibrio parahemolyticus septicaemia in a liver transplant patient: A case report","volume":"5","author":"Fernando","year":"2011","journal-title":"JMCR"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.micpath.2004.11.001","article-title":"\u2019In vivo\u2019 studies on the pathophysiological mechanism of vibrio parahaemolyticus tdh(+)\u2212induced secretion","volume":"38","author":"Baffone","year":"2005","journal-title":"Microb. Pathog."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1007\/s12275-012-2550-2","article-title":"The role of type iii secretion system 2 in vibrio parahaemolyticus pathogenicity","volume":"50","author":"Ham","year":"2012","journal-title":"J. Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1093\/ajcp\/71.4.476","article-title":"Wound infection associated with vibrio alginolyticus","volume":"71","author":"Pezzlo","year":"1979","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1017\/S095026889700798X","article-title":"Vibrio furnissii isolated from humans in Peru: A possible human pathogen?","volume":"119","author":"Dalsgaard","year":"1997","journal-title":"Epidemiology Infect."},{"key":"ref_16","first-page":"80","article-title":"Vibrio fluvialis (group f vibrio) in Maharashtra","volume":"76","author":"Thekdi","year":"1982","journal-title":"Indian J. Med. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3628","DOI":"10.3390\/ijerph7103628","article-title":"Vibrio fluvialis: An unusual enteric pathogen of increasing public health concern","volume":"7","author":"Igbinosa","year":"2010","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"ref_18","first-page":"3168","article-title":"Improving the knowledge on piper betle: Targeted metabolite analysis and effect on acetylcholinesterase","volume":"33","author":"Valentao","year":"2010","journal-title":"JSS"},{"key":"ref_19","first-page":"311","article-title":"Effect of ethanol extract of piper betle linn leaf on healing of nsaid-induced experimental ulcer--a novel role of free radical scavenging action","volume":"41","author":"Majumdar","year":"2003","journal-title":"Indian. J. Exp. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/1476-0711-9-7","article-title":"In vitro antifungal activity of hydroxychavicol isolated from piper betle l","volume":"9","author":"Ali","year":"2010","journal-title":"Ann. Clin. Microbiol. Antimicrob."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.rvsc.2007.03.006","article-title":"Ethnoveterinary study for antidermatophytic activity of piper betle, alpinia galanga and allium ascalonicum extracts in vitro","volume":"84","author":"Trakranrungsie","year":"2008","journal-title":"Res. Vet. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1211\/jpp.59.5.0012","article-title":"An ethanol extract of piper betle linn. Mediates its anti-inflammatory activity via down-regulation of nitric oxide","volume":"59","author":"Ganguly","year":"2007","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1039\/c2ib20206a","article-title":"Conserved host-pathogen ppis. Globally conserved inter-species bacterial ppis based conserved host-pathogen interactome derived novel target in c. Pseudotuberculosis, c. Diphtheriae, m. Tuberculosis, c. Ulcerans, y. Pestis, and e. Coli targeted by piper betel compounds","volume":"5","author":"Barh","year":"2013","journal-title":"Integr. Biol. (Camb)."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2731","DOI":"10.2174\/1568026619666190121105851","article-title":"Acetate kinase (ack) is essential for microbial growth and betel-derived compounds potentially target ack, phop and mdr proteins in m. Tuberculosis, v. Cholerae and pathogenic e. Coli: An in silico and in vitro study","volume":"18","author":"Tiwari","year":"2018","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4649","DOI":"10.1128\/AEM.66.11.4649-4654.2000","article-title":"Environmental investigations of vibrio parahaemolyticus in oysters after outbreaks in Washington, Texas, and New York (1997 and 1998)","volume":"66","author":"DePaola","year":"2000","journal-title":"Appl. Environ. Microb."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2194","DOI":"10.1128\/AEM.69.4.2194-2200.2003","article-title":"Pcr detection of a newly emerged pandemic vibrio parahaemolyticus o3:K6 pathogen in pure cultures and seeded waters from the gulf of Mexico","volume":"69","author":"Myers","year":"2003","journal-title":"Appl. Environ. Microb."},{"key":"ref_27","first-page":"110","article-title":"Pandemic vibrio parahaemolyticus o3:K6 on the american continent","volume":"3","year":"2014","journal-title":"Front. Microbiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1794","DOI":"10.1128\/AEM.06953-11","article-title":"Association of pandemic vibrio parahaemolyticus o3:K6 present in the coastal environment of northwest Mexico with cases of recurrent diarrhea between 2004 and 2010","volume":"78","year":"2012","journal-title":"Appl. Environ. Microb."},{"key":"ref_29","first-page":"221","article-title":"A pandemic vibrio parahaemolyticus o3:K6 clone causing most associated diarrhea cases in the pacific northwest coast of mexico","volume":"6","author":"Vidal","year":"2015","journal-title":"Front. Microbiol."},{"key":"ref_30","first-page":"635","article-title":"Isolation, characterization, and antibiotic resistance of vibrio spp. In sea turtles from northwestern Mexico","volume":"6","author":"Aguirre","year":"2015","journal-title":"Front. Microbiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1089\/mdr.2012.0127","article-title":"Virulence and multidrug resistance patterns of vibrio cholerae o1 isolates from diarrheal outbreaks of south india during 2006-2009","volume":"19","author":"Balaji","year":"2013","journal-title":"Microb. Drug Resist."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1099\/jmm.0.034744-0","article-title":"Multi-drug resistant vibrio cholerae o1 variant el tor isolated in northern vietnam between 2007 and 2010","volume":"61","author":"Tran","year":"2012","journal-title":"J. Med. Microbiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.trstmh.2005.07.007","article-title":"Fluoroquinolone-resistant vibrio cholerae isolated during a cholera outbreak in India","volume":"100","author":"Krishna","year":"2006","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_34","first-page":"269","article-title":"Prevalence and distribution of vibrio parahaemolyticus in finfish from cochin (south india)","volume":"48","author":"Sudha","year":"2012","journal-title":"Vet. Ital."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"380","DOI":"10.4315\/0362-028X.JFP-10-307","article-title":"Antimicrobial resistance of vibrio parahaemolyticus and vibrio alginolyticus strains isolated from farmed fish in korea from 2005 through 2007","volume":"74","author":"Oh","year":"2011","journal-title":"J. Food Prot."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.ijantimicag.2009.03.020","article-title":"Mechanism of drug resistance in a clinical isolate of vibrio fluvialis: Involvement of multiple plasmids and integrons","volume":"34","author":"Rajpara","year":"2009","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Mohanty, P., Patel, A., and Kushwaha Bhardwaj, A. (2012). Role of h- and d- mate-type transporters from multidrug resistant clinical isolates of vibrio fluvialis in conferring fluoroquinolone resistance. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0035752"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1093\/ajcp\/45.4_ts.493","article-title":"Antibiotic susceptibility testing by a standardized single disk method","volume":"45","author":"Bauer","year":"1966","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1128\/jb.1.3.321-331.1916","article-title":"The number of colonies allowable on satisfactory agar plates","volume":"1","author":"Breed","year":"1916","journal-title":"J. Bacteriol."},{"key":"ref_40","unstructured":"Moody, J.A., and Moody, J. (2007). Synergism Testing: Broth Microdilution Checkerboard and Broth Macrodilution Methods, ASM Press. [2nd ed.]."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/jac\/dkg301","article-title":"Synergy, antagonism, and what the chequerboard puts between them","volume":"52","author":"Odds","year":"2003","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"9046","DOI":"10.1021\/jf061679e","article-title":"Antioxidant activity of piper betel leaf extract and its constituents","volume":"54","author":"Rathee","year":"2006","journal-title":"J. Agric. Food Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"390","DOI":"10.4103\/0250-474X.43012","article-title":"Antimicrobial activity of terminalia catappa, manilkara zapota and piper betel leaf extract","volume":"70","author":"Nair","year":"2008","journal-title":"Indian. J. Pharm. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1002\/ptr.1564","article-title":"Antimicrobial activity of tiger\u2019s betel (piper porphyrophyllum n.E. Br., piperaceae)","volume":"18","author":"Wiart","year":"2004","journal-title":"Phytother. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.tibtech.2012.12.006","article-title":"Combination approaches to combat multidrug-resistant bacteria","volume":"31","author":"Worthington","year":"2013","journal-title":"Trend. Biotechnol."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/8\/2\/64\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:51:29Z","timestamp":1760187089000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/8\/2\/64"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,13]]},"references-count":45,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2019,6]]}},"alternative-id":["pathogens8020064"],"URL":"https:\/\/doi.org\/10.3390\/pathogens8020064","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,5,13]]}}}