Survival-strategies of endophytic Fusarium solani against indigenous camptothecin biosynthesis

The objective of this study was to investigate how the camptothecin (CPT) producing endophyte, Fusarium solani, ensures self-resistance before being incapacitated by its own and the host’s CPT biosynthesis. The primary structure of endophyte topoisomerase I (Topo 1, encoded by Top1 gene) was studied with emphasis on the CPT-binding and catalytic domains. Known Topo 1 amino acid residues conferring CPT resistance were screened in CPT-producing and CPT-lacking endophytes and the possible role of Topo 1 alteration in fungal resistance towards CPT was evaluated. Based on known nucleotide polymorphisms of Top1 associated with CPT resistance, the current findings indicate that fungal endophytes intrinsically possess resistance features against CPT produced by the associated host, irrespective of their indigenous biosynthetic capabilities. They might later develop further co-evolutionary resistance features against host and indigenous CPT. This study signifies the importance of resistance mechanisms employed by endophytes to tolerate toxic host-specific metabolites, and might provide deeper understanding of host–microbe co-evolution and further development of anticancer drugs.