Dual Function of Tropodithietic Acid as Antibiotic and Signaling Molecule in Quorum Sensing

The marine bacterium Phaeobacter inhibens produces tropodithietic acid (TDA), a broad-spectrum antibiotic and anticancer agent. TDA allows P. inhibens to antagonize other bacteria, including several pathogens, and eukaryotes. Since recently antibiotics are also discussed to function as intermicrobial signals. Here we show that ~10% of the genes of P. inhibens are strongly influenced by N-acyl-homoserine lactone (AHL) mediated quorum sensing (QS), switching the bacterium’s life style from attached to free-living. In an AHL negative mutant of P. inhibens subinhibitory concentrations of TDA caused the same regulatory effect as the AHL. This demonstrates that bacteria can produce antibiotic compounds not only as weapons, but also to substitute their endogenous AHL molecule in QS. The dual function of TDA probably supports the QS system to accelerate regulatory processes and points to a so far neglected role of antibiotics at subinhibitory concentrations in the environment and in microbial interactions. Comparison of whole transcriptomes of wildytype, quorum sensing mutants (pgaI and pgaR) and pgaI grown supplemented with subinhibitory concentration of the antibiotic TDA. RNA isolated in the late exponential growth phase. 4 biological replicates investigated for each strain.