In natural ecosystems where the self population density is low and food is scarce, AF production may confer competitive advantages, through inhibition of the growth of other organisms. It would be interesting to examine if other fungal JNJ-26481585 mw species also employ this survival strategy. We showed that no soluble AF biosynthesis inhibitor was released from the high spore density culture to media by using spent medium experiments, suggesting that A. flavus A3.2890 is somehow able to sense the population density and adjust their growth and AF production through cell-autonomous

machinery. Unlike Candidia albicans and Dictyostelium, where density factors are diffusible to media [53–55], we hypothesize that A. flavus may use a cell surface component to perceive such cultural density and nutrient signals. The possible role of G protein-mediated selleck products signaling [56] in this process is worth exploring. Alternatively, it has been reported that oxidative stress is a prerequisite for AF production Metabolism inhibitor [57]. It is plausible that the rapid growth in PMS media with high initial spore densities may lead to reduced intracellular oxygen availability and subsequently decreased oxidative stress, which could prevent AF production. It will be interesting to examine why this density-sensing machinery is active only when peptone, not glucose, is used as the carbon source. High initial spore densities repressed expression

of AF biosynthesis- related genes including aflS and aflR Transferring A. parasiticus mycelia from PMS to GMS media resulted in AF production, which is inhibited by cycloheximide or actinomycin D treatments, suggesting both de novo transcription and translation Baf-A1 clinical trial are required for AF biosynthesis

[23, 24]. In this study, we observed that high initial spore densities promoted mycelial growth but inhibited AF production, which is similar to the high temperature cultures in GMS media where no AFs are produced [58]. High temperature culture (37°C) specifically represses the expressions of AF biosynthesis genes without affecting expression of the transcriptional regulators aflR and aflS in the AF pathway gene cluster [20, 59, 60]. However, we found that high initial density cultures inhibited the expression of both the transcriptional regulators (aflR and aflS) and downstream AF biosynthesis genes simultaneously, suggesting a different manner of regulation. Further study is needed to elucidate if the density-dependent AF biosynthesis is regulated through antagonistic signaling pathways that coordinate vegetative growth, conidiation and AF production [2]. Cultures with high initial spore densities in PMS media trigger a metabolic shift from AF production to sugar metabolism Although primary and secondary metabolism share common transcriptional and translational machinery, secondary metabolism often commences during idiophase, when normal growth and development have ceased [61].