In every backyard, park, and playground on Earth, the ground is teeming with a type of bacteria called Streptomyces \u2014 one of the most abundant organisms on the planet. While these dirt-dwelling microbes are known for producing that earthy odour that fills the air after rainfall, that familiar scent is only the tip of their chemical-producing iceberg.<\/p>\n
Streptomyces are, in effect, natural pharmaceutical factories, responsible for producing many of the anticancer compounds, immunosuppressants and antibiotics used in clinics worldwide. But a new study published in the journal\u00a0Nature Microbiology<\/a> suggests that their chemical repertoire is even more complex than previously understood.<\/p>\n Researchers at McMaster University, Boston Children\u2019s Hospital, and Harvard Medical School, with collaborators from Stockholm University and Yale University, have identified and characterized a new class of Streptomyces-produced toxins that are very distantly related to the deadly toxin that causes diphtheria in humans.<\/p>\n Despite their structural similarities to the diphtheria toxin, these newly discovered toxic proteins do not cause human disease. They do, however, kill a broad range of insects.<\/p>\n \u201cThese toxins, which we\u2019ve called\u00a0Streptomyces\u00a0antiquus\u00a0insecticidal proteins, or\u00a0SAIPs, only affect insect cells,\u201d explains\u00a0Cameron Currie, a professor in McMaster\u2019s Department of Biochemistry and Biomedical Sciences and co-lead on the new study.<\/p>\n To understand exactly why SAIPs are only toxic to insects, researchers used a genome-editing technology called CRISPR to identify the host factors required for toxicity. By systematically knocking out the genes of insect cells, they pinpointed a surface protein called \u201cFlower.\u201d<\/p>\n While versions of this gene exist in other organisms, the insect-specific version is the only known receptor for SAIPs. These toxins cannot enter cells without it, which is why they have no effect on humans.<\/p>\n Through bioinformatic, genomic, and evolutionary analyses, the research team then traced the emergence of these previously unknown toxins through time, to determine when Streptomyces evolved the ability to produce them. They found that SAIPs are in fact ancient, dating back more than 100 million years.<\/p>\n For\u00a0Currie,\u00a0a member of the\u00a0Michael G. DeGroote Institute for Infectious Disease Research<\/a> and McMaster\u2019s Stephen A. Jarislowsky Chair in Pandemic Research<\/a>, the toxins\u2019 ancient history suggests a possibility that they have played a role in shaping human disease, although he notes that remains speculative.<\/p>\n \u201cWe know that the bacteria that causes diphtheria acquired its toxin\u00a0from another species of bacteria\u00a0long ago,\u00a0so it\u2019s possible that\u00a0these\u00a0Streptomyces\u00a0toxins were the crucible for the eventual emergence of the diphtheria toxin,\u201d\u00a0he says.<\/p>\n Crucially, not all species of Streptomyces produce these toxins \u2014 in fact, the vast majority of species live harmoniously in, on and around insects. The capability, researchers say, appears to be restricted to a few specific lineages within the massive genus.<\/p>\n \u201cStreptomyces have primarily been known to have mutualistic relationships with insects, but we have discovered a clade of strains that are likely insect pathogens,\u201d explains Min Dong, a researcher at Boston Children\u2019s Hospital, an associate professor at Harvard Medical School, and co-lead on the new study.<\/p>\n These\u00a0strains, researchers say,\u00a0have\u00a0evolved a\u00a0highly\u00a0specialized role\u00a0in nature.<\/p>\n \u201cThey don\u2019t just kill insects \u2014 they are also remarkably efficient at consuming them, using their dead hosts as a source of critical nutrients,\u201d says Currie, who also collaborated with Harvard\u2019s Norbert Perrimon on the study.<\/p>\n As these\u00a0specialized\u00a0Streptomyces\u00a0strains\u00a0break down insect tissue, they\u00a0simultaneously produce\u00a0potent antimicrobial\u00a0chemicals\u00a0\u2014\u00a0likely to\u00a0ward\u00a0off competing microbes drawn to the same resource.\u00a0As such, the research team believes that\u00a0these\u00a0insect-associated\u00a0strains of\u00a0Streptomyces\u00a0could be\u00a0a largely untapped\u00a0source of new antibiotics or other medically useful molecules.<\/p>\n Already, in past research,\u00a0the Currie Lab has\u00a0identified\u00a0a number of\u00a0promising antibiotics\u00a0produced by\u00a0other\u00a0Streptomyces\u00a0strains, which\u00a0makes\u00a0Currie\u00a0optimistic\u00a0about\u00a0the clinical\u00a0relevance\u00a0of\u00a0these new chemicals.<\/p>\n Beyond that,\u00a0Currie notes that\u00a0the discovery\u00a0of a SAIPs is\u00a0significant because\u00a0bacterial toxins\u00a0can\u00a0have implications\u00a0well\u00a0outside\u00a0of\u00a0their role in disease.\u00a0He notes that\u00a0botulinum toxin \u2014 commonly known as\u00a0botox\u00a0\u2014 has several medical and cosmetic applications, while other\u00a0bacterial\u00a0toxins have been harnessed for uses\u00a0in immunology, agriculture, and biotechnology.<\/p>\n \u201cRight now, this is a basic science discovery, but a discovery that may have some really practical applications in the future,\u201d he says.<\/p>\n \u201cA toxin like this could potentially help control vectors of human disease, like mosquitoes, which can transmit malaria and West Nile virus, or perhaps be used to protect crops from insect pests. It\u2019s possible it could be used in a number of different ways.\u201d<\/p>\n Currie and his collaborators have already patented their discovery and are now beginning to explore potential commercialization pathways for the toxin \u2014 particularly in agriculture, where insect toxins are typically in high demand.<\/p>\n In the meantime,\u00a0the research team is\u00a0investigating\u00a0how\u00a0SAIPs\u00a0behave in more complex biological settings, including\u00a0in\u00a0experimental systems involving crickets and mealworms\u00a0\u2014\u00a0organisms that serve as tractable models for studying infection\u00a0and\u00a0toxicity.<\/p>\n These studies are also allowing researchers to isolate\u00a0the\u00a0antimicrobials secreted\u00a0by\u00a0toxin-producing strains of\u00a0Streptomyces, which will help them better understand their\u00a0clinical potential.<\/p>\n But regardless of how that follow-on work\u00a0transpires, Currie says the\u00a0discovery alone\u00a0is a significant research achievement, and one that\u00a0signals\u00a0just how much\u00a0there is left to learn\u00a0about bacteria.<\/p>\n \u201cThat we have found something so novel in one of the\u00a0world\u2019s\u00a0most\u00a0abundant\u00a0and\u00a0well-studied groups of bacteria\u00a0underscores\u00a0how little we\u00a0actually\u00a0know about\u00a0them,\u201d\u00a0he says.<\/p>\n \u201cThis toxin stands as a powerful reminder that bacteria are incredibly diverse organisms,\u00a0with capabilities that continue to surprise us.\u201d<\/p>\n","protected":false},"excerpt":{"rendered":"In every backyard, park, and playground on Earth, the ground is teeming with a type of bacteria called…\n","protected":false},"author":2,"featured_media":639330,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[7],"tags":[49,48,66],"class_list":["post-639329","post","type-post","status-publish","format-standard","has-post-thumbnail","category-science","tag-ca","tag-canada","tag-science"],"_links":{"self":[{"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/posts\/639329","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/comments?post=639329"}],"version-history":[{"count":0,"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/posts\/639329\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/media\/639330"}],"wp:attachment":[{"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/media?parent=639329"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/categories?post=639329"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/tags?post=639329"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}