Aflatoxins and ochratoxins are among the most important mycotoxins of all and producers of both types of mycotoxins are present inAspergillussectionFlavi, albeit never in the same species. Some of the most efficient producers of aflatoxins and ochratoxins have not been described yet. Using a polyphasic approach combining phenotype, physiology, sequence and extrolite data, we describe here eight new species in sectionFlavi. Phylogenetically, sectionFlaviis split in eight clades and the section currently contains 33 species. Two species only produce aflatoxin B1 and B2 (A. pseudotamariiandA. togoensis), and 14 species are able to produce aflatoxin B1, B2, G1 and G2: three newly described speciesA. aflatoxiformans, A. austwickiiandA. cerealisin addition toA. arachidicola,A. minisclerotigenes,A. mottae, A. luteovirescens(formerlyA. bombycis), A. nomius, A. novoparasiticus, A. parasiticus, A. pseudocaelatus, A. pseudonomius, A. sergiiandA. transmontanensis. It is generally accepted thatA. flavusis unable to produce type G aflatoxins, but here we report on Korean strains that also produce aflatoxin G1 and G2. One strain ofA. bertholletiuscan produce the immediate aflatoxin precursor 3-O-methylsterigmatocystin, and one strain ofAspergillus sojaeand two strains ofAspergillus alliaceusproduced versicolorins. Strains of the domesticated forms ofA. flavusandA. parasiticus,A. oryzaeandA. sojae, respectively, lost their ability to produce aflatoxins, and from the remaining phylogenetically closely related species (belonging to theA. flavus-,A. tamarii-,A. bertholletius- andA. nomius-clades), onlyA. caelatus,A. subflavusandA. tamariiare unable to produce aflatoxins. With exception ofA. togoensisin theA. coremiiformis-clade, all species in the phylogenetically more distant clades (A. alliaceus-,A. coremiiformis-,A. leporis- andA. avenaceus-clade) are unable to produce aflatoxins. Three out of the four species in theA. alliaceus-clade can produce the mycotoxin ochratoxin A:A. alliaceus s.str. and two new species described here asA. neoalliaceusandA. vandermerwei. Eight species produced the mycotoxin tenuazonic acid:A. bertholletius,A. caelatus, A. luteovirescens,A. nomius, A. pseudocaelatus,A. pseudonomius, A. pseudotamariiandA. tamariiwhile the related mycotoxin cyclopiazonic acid was produced by 13 species:A. aflatoxiformans, A. austwickii, A. bertholletius, A. cerealis, A. flavus, A. minisclerotigenes, A. mottae, A. oryzae, A. pipericola, A. pseudocaelatus,A. pseudotamarii, A. sergiiandA. tamarii. Furthermore,A. hancockiiproduced speradine A, a compound related to cyclopiazonic acid. SelectedA. aflatoxiformans, A. austwickii, A. cerealis, A. flavus, A. minisclerotigenes, A. pipericolaandA. sergiistrains produced small sclerotia containing the mycotoxin aflatrem. Kojic acid has been found in all species in sectionFlavi, exceptA. avenaceusandA. coremiiformis. Only six species in the section did not produce any known mycotoxins:A. aspearensis,A. coremiiformis, A. lanosus, A. leporis, A. sojaeandA. subflavus. An overview of other small molecule extrolites produced inAspergillussectionFlaviis given.

In relation to emerging multiresistant bacteria, development of antimicrobials and new treatment strategies of infections should be expected to become a high-priority research area. Quorum sensing (QS), a communication system used by pathogenic bacteria likePseudomonas aeruginosato synchronize the expression of specific genes involved in pathogenicity, is a possible drug target. Previousin vitroandin vivostudies revealed a significant inhibition ofP. aeruginosaQS by crude garlic extract. By bioassay-guided fractionation of garlic extracts, we determined the primary QS inhibitor present in garlic to be ajoene, a sulfur-containing compound with potential as an antipathogenic drug. By comprehensivein vitroandin vivostudies, the effect of synthetic ajoene towardP. aeruginosawas elucidated. DNA microarray studies of ajoene-treatedP. aeruginosacultures revealed a concentration-dependent attenuation of a few but central QS-controlled virulence factors, including rhamnolipid. Furthermore, ajoene treatment ofin vitrobiofilms demonstrated a clear synergistic, antimicrobial effect with tobramycin on biofilm killing and a cease in lytic necrosis of polymorphonuclear leukocytes. Furthermore, in a mouse model of pulmonary infection, a significant clearing of infectingP. aeruginosawas detected in ajoene-treated mice compared to a nontreated control group. This study adds to the list of examples demonstrating the potential of QS-interfering compounds in the treatment of bacterial infections.

Quorum sensing (QS) communication systems are thought to afford bacteria with a mechanism to strategically cause disease. One example is Pseudomonas aeruginosa, which infects immunocompromised individuals such as cystic fibrosis patients. The authors have previously documented that blockage of the QS systems not only attenuates Ps. aeruginosa but also renders biofilms highly susceptible to treatment with conventional antibiotics. Filamentous fungi produce a battery of secondary metabolites, some of which are already in clinical use as antimicrobial drugs. Fungi coexist with bacteria but lack active immune systems, so instead rely on chemical defence mechanisms. It was speculated that some of these secondary metabolites could interfere with bacterial QS communication. During a screening of 100 extracts from 50 Penicillium species, 33 were found to produce QS inhibitory (QSI) compounds. In two cases, patulin and penicillic acid were identified as being biologically active QSI compounds. Their effect on QS-controlled gene expression in Ps. aeruginosa was verified by DNA microarray transcriptomics. Similar to previously investigated QSI compounds, patulin was found to enhance biofilm susceptibility to tobramycin treatment. Ps. aeruginosa has developed QS-dependent mechanisms that block development of the oxidative burst in PMN neutrophils. Accordingly, when the bacteria were treated with either patulin or penicillic acid, the neutrophils became activated. In a mouse pulmonary infection model, Ps. aeruginosa was more rapidly cleared from the mice that were treated with patulin compared with the placebo group.

This review presents an update on the current knowledge of the secondary metabolite potential of the major fungal species used in industrial biotechnology, i.e., Aspergillus niger, Aspergillus oryzae, and Trichoderma reesei. These species have a long history of safe use for enzyme production. Like most microorganisms that exist in a challenging environment in nature, these fungi can produce a large variety and number of secondary metabolites. Many of these compounds present several properties that make them attractive for different industrial and medical applications. A description of all known secondary metabolites produced by these species is presented here. Mycotoxins are a very limited group of secondary metabolites that can be produced by fungi and that pose health hazards in humans and other vertebrates when ingested in small amounts. Some mycotoxins are species-specific. Here, we present scientific basis for (1) the definition of mycotoxins including an update on their toxicity and (2) the clarity on misclassification of species and their mycotoxin potential reported in literature, e.g., A. oryzae has been wrongly reported as an aflatoxin producer, due to misclassification of Aspergillus flavus strains. It is therefore of paramount importance to accurately describe the mycotoxins that can potentially be produced by a fungal species that is to be used as a production organism and to ensure that production strains are not capable of producing mycotoxins during enzyme production. This review is intended as a reference paper for authorities, companies, and researchers dealing with secondary metabolite assessment, risk evaluation for food or feed enzyme production, or considerations on the use of these species as production hosts.