Pollen Streptomyces Produce Antibiotic That Inhibits the Honey Bee Pathogen Paenibacillus larvae

Humans use natural products to treat disease; similarly, some insects use natural products produced by Actinobacteria to combat infectious pathogens. Honey bees, Apis mellifera, are ecologically and economically important for their critical role as plant pollinators and are host to diverse and potentially virulent pathogens that threaten hive health. Here, we provide evidence that Actinobacteria that can suppress pathogenic microbes are associated with A. mellifera. We show through culture-dependent approaches that Actinobacteria in the genus Streptomyces are commonly isolated from foraging bees, and especially common in pollen stores. One strain, isolated from pollen stores, exhibited pronounced inhibitory activity against Paenibacillus larvae, the causative agent of American foulbrood. Bioassay-guided HPLC fractionation, followed by NMR and mass spectrometry, identified the known macrocyclic polyene lactam, piceamycin that was responsible for this activity. Further, we show that in its purified form, piceamycin has potent inhibitory activity toward P. larvae. Our results suggest that honey bees may use pollen-derived Actinobacteria and their associated small molecules to mediate colony health. Given the importance of honey bees to modern agriculture and their heightened susceptibility to disease, the discovery and development of antibiotic compounds from hives could serve as an important strategy in supporting disease management within apiaries.National Institute for Health/[U19 AI142720]/NIH/Estados UnidosNational Institute of Food and Agriculture/[WISO1321]/NIFA/Estados UnidosUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Básicas::Centro de Investigación en Estructuras Microscópicas (CIEMIC)UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Básicas::Centro de Investigación en Biología Celular y Molecular (CIBCM

Microtermolides A and B from Termite-Associated Streptomyces sp. and Structural Revision of Vinylamycin

Microtermolides A (1) and B (2) were isolated from a Streptomyces sp. strain associated with fungus-growing termites. The structures of 1 and 2 were determined by 1D- and 2D-NMR spectroscopy and high-resolution mass spectrometry. Structural elucidation of 1 led to the re-examination of the structure originally proposed for vinylamycin (3). Based on a comparison of predicted and experimental $^1$H and $^{13}$C NMR chemical shifts, we propose that vinylamycin’s structure be revised from 3 to 4

Tryptorubin A: A Polycyclic Peptide from a Fungus-Derived Streptomycete

Fungus-growing ants engage in complex symbiotic relationships with their fungal crop, specialized fungal pathogens, and bacteria that provide chemical defenses. In an effort to understand the evolutionary origins of this multilateral system, we investigated bacteria isolated from fungi. One bacterial strain (Streptomyces sp. CLI2509) from the bracket fungus Hymenochaete rubiginosa, produced an unusual peptide, tryptorubin A, which contains heteroaromatic links between side chains that give it a rigid polycyclic globular structure. The three-dimensional structure was determined by NMR and MS, including a 13C-13C COSY of isotopically enriched material, degradation, derivatives, and computer modeling. Whole genome sequencing identified a likely pair of biosynthetic genes responsible for tryptorubin A’s linear hexapeptide backbone. The genome also revealed the close relationship between CLI2509 and Streptomyces sp. SPB78, which was previously implicated in an insect–bacterium symbiosis

Host control of symbiont natural product chemistry in cryptic populations of the tunicate Lissoclinum patella.

Natural products (secondary metabolites) found in marine invertebrates are often thought to be produced by resident symbiotic bacteria, and these products appear to play a major role in the symbiotic interaction of bacteria and their hosts. In these animals, there is extensive variation, both in chemistry and in the symbiotic bacteria that produce them. Here, we sought to answer the question of what factors underlie chemical variation in the ocean. As a model, we investigated the colonial tunicate Lissoclinum patella because of its rich and varied chemistry and its broad geographic range. We sequenced mitochondrial cytochrome c oxidase 1 (COXI) genes, and found that animals classified as L. patella fall into three phylogenetic groups that may encompass several cryptic species. The presence of individual natural products followed the phylogenetic relationship of the host animals, even though the compounds are produced by symbiotic bacteria that do not follow host phylogeny. In sum, we show that cryptic populations of animals underlie the observed chemical diversity, suggesting that the host controls selection for particular secondary metabolite pathways. These results imply novel approaches to obtain chemical diversity from the oceans, and also demonstrate that the diversity of marine natural products may be greatly impacted by cryptic local extinctions

Activation of the Nuclear Factor E2-Related Factor 2 Pathway by Novel Natural Products Halomadurones A–D and a Synthetic Analogue

Two novel chlorinated pyrones, halomadurones A and B, and two novel brominated analogues, halomadurones C and D, were isolated from a marine Actinomadura sp. cultivated from the ascidian Ecteinascidia turbinata. Additionally, a non-halogenated analogue, 2-methyl-6-((E)-3-methyl-1,3-hexadiene)-γ-pyrone, was synthesized to understand the role of the halogens for activity. Halomadurones C and D demonstrated potent nuclear factor E2-related factor antioxidant response element (Nrf2-ARE) activation, which is an important therapeutic approach for treatment of neurodegenerative diseases

Brackish habitat dictates cultivable Actinobacterial diversity from marine sponges.

Bacterial communities associated with marine invertebrates such as sponges and ascidians have demonstrated potential as sources of bio-medically relevant small molecules. Metagenomic analysis has shown that many of these invertebrates harbor populations of Actinobacteria, many of which are cultivable. While some populations within invertebrates are transmitted vertically, others are obtained from the environment. We hypothesized that cultivable diversity from sponges living in brackish mangrove habitats have associations with Actinobacterial populations that differ from those found in clear tropical waters. In this study, we analyzed the cultivable Actinobacterial populations from sponges found in these two distinct habitats with the aim of understanding the secondary metabolite potential. Importantly, we wanted to broadly evaluate the potential differences among these groups to guide future Actinobacterial collection strategies for the purposes of drug discovery

Peptidolipins B–F, Antibacterial Lipopeptides from an Ascidian-Derived <i>Nocardia</i> sp.

A marine <i>Nocardia</i> sp. isolated from the ascidian <i>Trididemnum orbiculatum</i> was found to produce five new lipopeptides, peptidolipins B–F (<b>1</b>–<b>5</b>), which show distinct similarities to the previously reported l-Val­(6) analog of peptidolipin NA. Synthetic modification of peptidolipin E (<b>4</b>) was used to determine the location of an olefin within the lipid chain. The advanced Marfey’s method was used to determine the absolute configurations of the amino acids. Peptidolipins B (<b>1</b>) and E (<b>4</b>) demonstrated moderate antibacterial activity against methicillin-resistant <i>Staphylococcus aureus</i> and methicillin-sensitive <i>Staphylococcus aureus</i>