Dataset Information

Genome Mining for Antimicrobial Compounds in Wild Marine Animals-Associated Enterococci.

ABSTRACT: New ecosystems are being actively mined for new bioactive compounds. Because of the large amount of unexplored biodiversity, bacteria from marine environments are especially promising. Further, host-associated microbes are of special interest because of their low toxicity and compatibility with host health. Here, we identified and characterized biosynthetic gene clusters encoding antimicrobial compounds in host-associated enterococci recovered from fecal samples of wild marine animals remote from human-affected ecosystems. Putative biosynthetic gene clusters in the genomes of 22 Enterococcus strains of marine origin were predicted using antiSMASH5 and Bagel4 bioinformatic software. At least one gene cluster encoding a putative bioactive compound precursor was identified in each genome. Collectively, 73 putative antimicrobial compounds were identified, including 61 bacteriocins (83.56%), 10 terpenes (13.70%), and 2 (2.74%) related to putative nonribosomal peptides (NRPs). Two of the species studied, Enterococcus avium and Enterococcus mundtti, are rare causes of human disease and were found to lack any known pathogenic determinants but yet possessed bacteriocin biosynthetic genes, suggesting possible additional utility as probiotics. Wild marine animal-associated enterococci from human-remote ecosystems provide a potentially rich source for new antimicrobial compounds of therapeutic and industrial value and potential probiotic application.

SUBMITTER: Prichula J

PROVIDER: S-EPMC8229437 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Genome Mining for Antimicrobial Compounds in Wild Marine Animals-Associated Enterococci.

Prichula Janira J Primon-Barros Muriel M Luz Romeu C Z RCZ Castro Ícaro M S ÍMS Paim Thiago G S TGS Tavares Maurício M Ligabue-Braun Rodrigo R d'Azevedo Pedro A PA Frazzon Jeverson J Frazzon Ana P G APG Seixas Adriana A Gilmore Michael S MS

Marine drugs 20210606 6

New ecosystems are being actively mined for new bioactive compounds. Because of the large amount of unexplored biodiversity, bacteria from marine environments are especially promising. Further, host-associated microbes are of special interest because of their low toxicity and compatibility with host health. Here, we identified and characterized biosynthetic gene clusters encoding antimicrobial compounds in host-associated enterococci recovered from fecal samples of wild marine animals remote fro ...[more]

PMID: 34204046

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Project description:Enterococci are commensals that proliferated as animals crawled ashore hundreds of millions of years ago. They are also leading causes of multidrug-resistant hospital-acquired infections. While most studies are driven by clinical interest, comparatively little is known about enterococci in the wild or the effect of human activity on them. Pharmaceutical pollution and runoff from other human activities are encroaching widely into natural habitats. To assess their reach into remote habitats, we investigated the identity, genetic relatedness, and presence of specific traits among 172 enterococcal isolates from wild Magellanic penguins. Four enterococcal species, 18 lineage groups, and different colonization patterns were identified. One Enterococcus faecalis lineage, sequence type 475 (ST475), was isolated from three different penguins, making it of special interest. Its genome was compared to those of other E. faecalis sequence types (ST116 and ST242) recovered from Magellanic penguins, as well as to an existing phylogeny of E. faecalis isolated from diverse origins over the past 100 years. No penguin-derived E. faecalis strains were closely related to dominant clinical lineages. Most possessed intact CRISPR defenses, few mobile elements, and antibiotic resistances limited to those intrinsic to the species and lacked pathogenic features conveyed by mobile elements. Interestingly, plasmids were identified in penguin isolates that also had been reported for other marine mammals. Enterococci isolated from penguins showed limited anthropogenic impact, indicating that they are likely representative of those naturally circulating in the ecosystem inhabited by the penguins. These findings establish an important baseline for detecting the encroachment of human activity into remote planetary environments.IMPORTANCE Enterococci are host-associated microbes that have an unusually broad range, from the built hospital environment to the guts of insects and other animals in remote locations. Despite their occurrence in the guts of animals for hundreds of millions of years, we know little about the properties that confer this range or how anthropogenic activities may be introducing new selective forces. Magellanic penguins live at the periphery of human habitation. It was of interest to examine enterococci from these animals for the presence of antibiotic resistance and other markers reflective of anthropogenic selection. Diverse enterococcal lineages found discount the existence of a single well-adapted intrinsic penguin-specific species. Instead, they appear to be influenced by a carnivorous lifestyle and enterococci present in the coastal sea life consumed. These results indicate that currently, the penguin habitat remains relatively free of pollutants that select for adaptation to human-derived stressors.

Project description:IntroductionAntimicrobial resistance (AMR) is a global health concern, occurring when bacteria evolve to render antimicrobials no longer effective. Antimicrobials have important roles in beef production; however, the potential to introduce AMR to people through beef products is a concern. This scoping review identifies factors associated with changes in the prevalence of antimicrobial-resistant Enterococcus spp. applicable to the Canadian farm-to-fork beef continuum.MethodsFive databases (MEDLINE, BIOSIS, Web of Science, Embase, and CAB Abstracts) were searched for articles published from January 1984 to March 2022, using a priori inclusion criteria. Peer-reviewed articles were included if they met all the following criteria: written in English, applicable to the Canadian beef production context, primary research, in vivo research, describing an intervention or exposure, and specific to Enterococcus spp.ResultsOut of 804 screened articles, 26 were selected for inclusion. The included articles discussed 37 factors potentially associated with AMR in enterococci, with multiple articles discussing at least two of the same factors. Factors discussed included antimicrobial administration (n = 16), raised without antimicrobials (n = 6), metal supplementation (n = 4), probiotics supplementation (n = 3), pen environment (n = 2), essential oil supplementation (n = 1), grass feeding (n = 1), therapeutic versus subtherapeutic antimicrobial use (n = 1), feeding wet distiller grains with solubles (n = 1), nutritional supplementation (n = 1) and processing plant type (n = 1). Results were included irrespective of their quality of evidence.DiscussionComparability issues arising throughout the review process were related to data aggregation, hierarchical structures, study design, and inconsistent data reporting. Findings from articles were often temporally specific in that resistance was associated with AMR outcomes at sampling times closer to exposure compared to studies that sampled at longer intervals after exposure. Resistance was often nuanced to unique gene and phenotypic resistance patterns that varied with species of enterococci. Intrinsic resistance and interpretation of minimum inhibitory concentration varied greatly among enterococcal species, highlighting the importance of caution when comparing articles and generalizing findings.Systematic review registration[http://hdl.handle.net/1880/113592].

Project description:Complex pathological diseases, such as cancer, infection, and Alzheimer's, need to be targeted by multipronged curative. Various omics technologies, with a high rate of data generation, demand artificial intelligence to translate these data into druggable targets. In this study, 82 marine venomous animal species were retrieved, and 3505 cryptic cell-penetrating peptides (CPPs) were identified in their toxins. A total of 279 safe peptides were further analyzed for antimicrobial, anticancer, and immunomodulatory characteristics. Protease-resistant CPPs with endosomal-escape ability in Hydrophis hardwickii, nuclear-localizing peptides in Scorpaena plumieri, and mitochondrial-targeting peptides from Synanceia horrida were suitable for compartmental drug delivery. A broad-spectrum S. horrida-derived antimicrobial peptide with a high binding-affinity to bacterial membranes was an antigen-presenting cell (APC) stimulator that primes cytokine release and naïve T-cell maturation simultaneously. While antibiofilm and wound-healing peptides were detected in Synanceia verrucosa, APC epitopes as universal adjuvants for antiviral vaccination were in Pterois volitans and Conus monile. Conus pennaceus-derived anticancer peptides showed antiangiogenic and IL-2-inducing properties with moderate BBB-permeation and were defined to be a tumor-homing peptide (THP) with the ability to inhibit programmed death ligand-1 (PDL-1). Isoforms of RGD-containing peptides with innate antiangiogenic characteristics were in Conus tessulatus for tumor targeting. Inhibitors of neuropilin-1 in C. pennaceus are proposed for imaging probes or therapeutic delivery. A Conus betulinus cryptic peptide, with BBB-permeation, mitochondrial-targeting, and antioxidant capacity, was a stimulator of anti-inflammatory cytokines and non-inducer of proinflammation proposed for Alzheimer's. Conclusively, we have considered the dynamic interaction of cells, their microenvironment, and proportional-orchestrating-host- immune pathways by multi-target-directed CPPs resembling single-molecule polypharmacology. This strategy might fill the therapeutic gap in complex resistant disorders and increase the candidates' clinical-translation chance.

Dataset Information

Genome Mining for Antimicrobial Compounds in Wild Marine Animals-Associated Enterococci.

Publications

Genome Mining for Antimicrobial Compounds in Wild Marine Animals-Associated Enterococci.

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