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Abstract

The increasing resistance of human pathogens severely limits the
efficacy of antibiotics in medicine, yet many animals, including
solitary beewolf wasps, successfully engage in defensive alliances
with antibiotic-producing bacteria for millions of years. Here, we
report on the in situ production of 49 derivatives belonging to
three antibiotic compound classes (45 piericidin derivatives, 3
streptochlorin derivatives, and nigericin) by the symbionts of 25 beewolf
host species and subspecies, spanning 68 million years of
evolution. Despite a high degree of qualitative stability in the antibiotic
mixture, we found consistent quantitative differences between species
and across geographic localities, presumably reflecting adaptations to
combat local pathogen communities. Antimicrobial bioassays with the
three main components and in silico predictions based on the structure
and specificity in polyketide synthase domains of the piericidin
biosynthesis gene cluster yield insights into the mechanistic basis and
ecoevolutionary implications of producing a complex mixture of
antimicrobial compounds in a natural setting.