Why antibiotics: A comparative evaluation of different hypotheses for the natural role of antibiotics and an evolutionary synthesis

Abstract

Although secondary metabolites with antimicrobial and other bioactivities are explored extensively, the natural or ecological role(s) of secondary metabolites is not yet clearly known. We review here the different hypotheses for the ecological role of antibiotics, with particular focus on the genus Streptomyces which is unparalleled in the richness of secondary metabolites. We first lay down our expectations from an ecological hypothesis for antibiotics and then weigh the six predominant hypotheses against them including antibiotics as weapons in competition, as aid in sporulation, as bartered benefits in symbioses, as signal molecules in community homeostasis, as weapons in predation and as metabolic waste or bi-products. The analysis shows that no single hypothesis meets all the expectations. While the waste or bi-product hypothesis can safely be eliminated all others have some evidence in support. It is possible therefore that antibiotics serve a multitude of ecological functions and it is possible to visualize a pathway for the radiating functions. According to this synthesis antibiotics evolved primarily as weapons in predation on other microorganisms. The inevitable co-evolution with prey species led to diversification of the genes and pathways. Some of the secondary metabolites eventually radiated to acquire other functions such as competition between predators. Some secondary metabolites evolved animal toxicity as a mutualistic barter to protect the symbiotic partner from grazing/predation by animals. Transcription modulation primarily evolved as activation of defense mechanisms by the prey which may have later radiated to serve interspecies signaling functions. The synthesis successfully links different functions of antibiotics with logical coherence.