Lenzimycins A and B, Metabolites With Antibacterial Properties From Brevibacillus sp. Associated With the Dung Beetle Onthophagus lenzii.

Joon Soo An,Byung-Yong Kim,Suk Won Kim,Shin-Il Jo,Donghee Woo,Jongheon Shin,Dong-Chan Oh,Ki-Bong Oh,Hee-Jeon Hong,Elisabeth Somers,Seong-Heon Hong,Jayho Lee

doi:10.3389/fmicb.2020.599911

Joon Soo An, Byung-Yong Kim + Show 10 more

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https://doi.org/10.3389/fmicb.2020.599911

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Abstract

Symbiotic microorganisms associated with insects can produce a wide array of metabolic products, which provide an opportunity for the discovery of useful natural products. Selective isolation of bacterial strains associated with the dung beetle, Onthophagus lenzii, identified two strains, of which the antibiotic-producing Brevibacillus sp. PTH23 inhibited the growth of Bacillus sp. CCARM 9248, which is most closely related to the well-known entomopathogen, Bacillus thuringiensis. A comprehensive chemical investigation based on antibiotic activity discovered two new antibiotics, named lenzimycins A and B (1-2), which inhibited growth of Bacillus sp. CCARM 9248. The 1H and 13C NMR, MS, MS/MS, and IR analyses elucidated the structures of 1 and 2, which comprised a novel combination of fatty acid (12-methyltetradecanoic acid), glycerol, sulfate, and N-methyl ethanolamine. Furthermore, the acid hydrolysis of 1 revealed the absolute configuration of 12-methyltetradecanoic acid as 12S by comparing its optical rotation value with authentic (R)- and (S)-12-methyltetradecanoic acid. In addition to inhibition of Bacillus sp. CCARM 9248, lenzimycins A and B were found to inhibit the growth of some human pathogenic bacteria, including Enterococcus faecium and certain strains of Enterococcus faecalis. Furthermore, the present study elucidated that lenzimycins A and B activated a reporter system designed to detect the bacterial cell envelope stress, thereby indicating an activity against the integrity of the bacterial cell wall.

Highlights

Insects harbor symbiotic or pathogenic microorganisms; they have gained increasing interest as a reservoir for biotechnologically and pharmaceutically important microbes (Bode, 2010)
Sequencing of the 16S rRNA genes and phylogenetic analysis revealed that the strains PTH23 and CCARM9248 shared high similarity with Brevibacillus brevis NBRC 15304T (100%) and B. thuringiensis ATCC 10792T (99.8%), respectively (Supplementary Figures S16, S17)
The analyses showed markedly narrowspectrum antibiotic effects as they were effective against only a few Enterococcus strains such as vancomycin-resistant E. faecium (VREF: vanA) with minimal inhibitory concentration (MIC) values of 0.5 ∼ 1.0 μg/mL, E. faecium ATCC 19434 with MIC values of 8.0 ∼ 16 μg/mL, and an S. aureus strain CCARM 0205 with MIC values of 32 ∼ 64 μg/mL (Table 2A)

Summary

Introduction

Insects harbor symbiotic or pathogenic microorganisms; they have gained increasing interest as a reservoir for biotechnologically and pharmaceutically important microbes (Bode, 2010). Chemical ecological investigation of attine ants, Acromyrmex rugosus and their symbionts revealed a combination of antifungal compounds that inhibited the specialized fungal pathogen, Escovopsis. These small bacterial molecules were evaluated as inhibitors against the human protozoan parasite Leishmania donovani (Ortega et al, 2019). It has been reported that the symbiotic Streptomyces bacteria, located in specialized antennal glands, excrete antibiotics to protect wasp larvae from pathogenic fungal infestation (Kaltenpoth et al, 2005; Kroiss et al, 2010). Studies have shown that the stingless bees, Melipona scutellaris, engage in defensive symbiosis with actinobacteria that produce antibacterial small molecules including the lobophorin, anthracycline, and cyclic hexadepsipeptide families, helping to protect their colonies against the entomopathogenic Paenibacillus larvae (Rodríguez-Hernández et al, 2019; Menegatti et al, 2020)

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