Abstract

Identifying new sources for small molecule discovery is necessary to help mitigate the continuous emergence of antibiotic-resistance in pathogenic microbes. Recent studies indicate that one potentially rich source of novel natural products is Actinobacterial symbionts associated with social and solitary Hymenoptera. Here we test this possibility by examining two species of solitary mud dauber wasps, Sceliphron caementarium and Chalybion californicum. We performed enrichment isolations from 33 wasps and obtained more than 200 isolates of Streptomyces Actinobacteria. Chemical analyses of 15 of these isolates identified 11 distinct and structurally diverse secondary metabolites, including a novel polyunsaturated and polyoxygenated macrocyclic lactam, which we name sceliphrolactam. By pairing the 15 Streptomyces strains against a collection of fungi and bacteria, we document their antifungal and antibacterial activity. The prevalence and anti-microbial properties of Actinobacteria associated with these two solitary wasp species suggest the potential role of these Streptomyces as antibiotic-producing symbionts, potentially helping defend their wasp hosts from pathogenic microbes. Finding phylogenetically diverse and chemically prolific Actinobacteria from solitary wasps suggests that insect-associated Actinobacteria can provide a valuable source of novel natural products of pharmaceutical interest.

Highlights

  • Small molecules derived from natural sources play a key role in human welfare, serving as drugs or drug precursors with useful pharmaceutical properties [1,2]

  • Our findings show that diverse Actinobacteria in the genus Streptomyces can be readily isolated from a few individuals of a single insect group

  • Isolations from eight C. californicum and 25 S. caementarium yielded more than 200 strains of Streptomyces representing 24 distinct morphotypes

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Summary

Introduction

Small molecules derived from natural sources play a key role in human welfare, serving as drugs or drug precursors with useful pharmaceutical properties [1,2] Among these natural products, antibiotics are important, abating human suffering and death from infectious disease [1,3]. Current strategies for addressing the urgent need for new antibiotics include metabolic engineering, synthetic chemistry, and genomic or metagenomic approaches [2,7,8,9,10,11,12,13] Another approach is identifying sources of microbes that have not been explored for their potential natural products [5,6,14,15,16,17,18,19,20,21]

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