Antibacterial effect of the bioactive compound beauvericin produced by Fusarium proliferatum on solid medium of wheat G. Meca a, * , I. Sospedra a , J.M. Soriano a , A. Ritieni b , A. Moretti c , J. Mañes a a Laboratory of Food Chemistry and Toxicology, Faculty of Pharmacy, University of Valencia, Av. Vicent Andrés Estellés s/n, 46100 Burjassot, Spain b Department of Food Science. University of Naples “Federico II”, Via Universitá 100, 80055, Portici, Napoli, Italy c CNR (Research National Council), ISPA Institute of Science of Food Production, Via Amendola 122/O, Bari, Italy article info Article history: Received 2 December 2009 Received in revised form 22 March 2010 Accepted 25 March 2010 Available online 3 April 2010 Keywords: Beauvericin Mycotoxins Fusarium proliferatum High performance liquid chromatography Mass spectrometry Antibacterial effects abstract To obtain the bioactive compound beauvericin (BEA), Fusarium proliferatum CECT 20569 was grown on a solid medium of wheat, utilizing the technique of the solid state fermentation (SSF), being this mycotoxin purified by high performance liquid chroma- tography (HPLC) with a reverse phase semi-preparative column using as the mobile phase acetonitrile/water in gradient condition. The purity of the BEA was verified by analytical HPLC and liquid chromatography tandem mass spectrometry (LC/MS-MS). The pure frac- tions of BEA were utilized to determinate the antibiotic effects on several bacterial strains that are considered normally pathogens of the intestinal tract as: Escherichia coli, Entero- coccus faecium, Salmonella enterica, Shigella dysenteriae, Listeria monocytogenes, Yersinia enterocolitica, Clostridium perfringens, Pseudomonas aeruginosa and Staphylococcus aureus. Ó 2010 Elsevier Ltd. All rights reserved. 1. Introduction Mycotoxins are naturally occurring secondary metabo- lites produced by the mycelial structures of either toxigenic or nontoxigenic filamentous fungi (Paciolla et al., 2008). Beauvericin (BEA) is a depsipeptide that was first identified in a soil-borne entomopathogenic (insect-pathogenic) fungus Beauveria bassiana, which was recognized as the causative agent for heavy losses of the European sericulture in the 16th and 17th centuries (Tang et al., 2005). Nowadays, BEA is considered to be a putative mycotoxin (toxic fungal metabolite) that may affect human and animal health, since it is also produced by many species of the fungus Fusarium that infect important cereal grains such as corn, rice, and wheat (Desjardins et al., 2000; Logrieco et al., 1993a). The potential mycotoxic role of BEA is exemplified by results from in vitro studies using cell lines. For instance, BEA induces significant cell deaths in insect, murine, and human tumor cell lines (Mazziotti and Perlmutter, 1998; Calo et al., 2003). Furthermore, BEA is a potent and specific cholesterol acyltransferase inhibitor in rat liver microsomes (Tomoda et al., 1992). In mammalian cell lines, cell deaths caused by BEA have been suggested to involve a Ca 2þ dependent pathway, in which BEA induces a significant increase in intracellular Ca 2þ concentration that leads death cell as a result of a combination of both apoptosis and necrosis (Logrieco et al., 1998; Nilanonta et al., 2002; Jow et al., 2004; Lin et al., 2005; Ojcius et al., 1991). The mechanism of BEA-induced Ca 2þ increase, however, remains inconclusive. BEA-induced apoptotic changes such as DNA fragmentation have been demonstrated to take place in the complete absence of extracellular Ca 2þ (Ojcius et al., 1991), suggesting that BEA triggers release of Ca 2þ from internal Ca 2þ stores. In fact, BEA has since been regarded as an apoptotic agent that releases Ca 2þ exclu- sively from endoplasmic reticulum (Lin et al., 2005). BEA has exhibited minimum inhibitory concentration (MIC) values of 0.8e1.6 mg/mL against Mycobacterium tuberculosis, and IC 50 values of 1.3e2.4 mg/mL against Plas- modium falciparium (Nilanonta et al., 2002). In a recent * Corresponding author. Tel.: þ34963544959; fax: þ3496354954. E-mail address: giuseppe.meca@uv.es (G. Meca). Contents lists available at ScienceDirect Toxicon journal homepage: www.elsevier.com/locate/toxicon 0041-0101/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.toxicon.2010.03.022 Toxicon 56 (2010) 349e354