Bacteria Associated With Shiraia Fruiting Bodies Influence Fungal Production of Hypocrellin A

Abstract

Hypocrellin A (HA) is a natural red perylenequinone pigment from <i>Shiraia</i> fruiting body, which was used clinically on various skin diseases and developed as a photodynamic therapy agent against cancers. The fruiting bodies may harbor a diverse but poorly understood microbial community. In this study, we characterized the bacterial community of <i>Shiraia</i> fruiting body using a combination of culture-based method and Illumina high-throughput sequencing, and tested the involvement of some companion bacteria in fungal HA production using the fungal-bacterial confrontation assay. Our results revealed that the bacterial community in the fruiting body was dominated by <i>Bacillus</i> and <i>Pseudomonas</i>. Some <i>Pseudomonas</i> isolates such as <i>P. fulva</i>, <i>P. putida</i>, and <i>P. parafulva</i> could stimulate fungal HA accumulation by <i>Shiraia</i> sp. S9. The bacterial treatment of <i>P. fulva</i> SB1 up-regulated the expression of polyketide synthase (<i>PKS</i>) for HA biosynthesis and transporter genes including ATP-binding cassette (<i>ABC</i>) and major facilitator superfamily transporter (<i>MFS</i>) for HA exudation. After the addition of live <i>P. fulva</i> SB1, the mycelium cultures of <i>Shiraia</i> sp. S9 presented a higher HA production (225.34 mg/L), about 3.25-fold over the mono-culture. On the other hand, <i>B. cereus</i> was capable of alleviating fungal self-toxicity from HA <i>via</i> down-regulation of HA biosynthetic genes or possible biodegradation on HA. To our knowledge, this is the first report on the diversified species of bacteria associated with <i>Shiraia</i> fruiting bodies and the regulation roles of the companion bacteria on fungal HA biosynthesis. Furthermore, the bacterial co-culture provided a good strategy for the enhanced HA production by <i>Shiraia</i>.