Staphylococcus aureus lipid factors modulate melanoma clustering and invasion in zebrafish

The microbiome can influence cancer development and progression. However, less is known about the role of the skin microbiota in melanoma. Here, we take advantage of a zebrafish melanoma model to probe the effects of Staphylococcus aureus on melanoma invasion. We find that S. aureus produces factors that enhance melanoma invasion and dissemination in zebrafish larvae. We used a published in vitro 3D cluster formation assay which correlates increased clustering with tumor invasion. S. aureus supernatant increased clustering of melanoma cells which was abrogated by use of a Rho-Kinase inhibitor, implicating a role for Rho-GTPases. The melanoma clustering response was specific to S. aureus and not other staphylococcal species, including S. epidermidis. Our findings suggest that S. aureus may promote melanoma clustering and invasion via lipids generated by the lipase SAL2 (gehB). Taken together, these findings suggest that specific bacterial products mediate melanoma invasive migration in zebrafish. Summary statementS. aureus supernatant increases melanoma invasion in zebrafish and is likely mediated by production of bacterial lipids.