Burkholderia species in sugarcane: the relationship among antifungal production, intrinsic antimicrobial resistance, and pest biocontrol

伯克霍尔德氏菌科（Burkholderiaceae）包括广泛分布在地球上的环境细菌家族，其存在于不同的环境中并与植物、昆虫、动物和人类相关联，并且还显示出非常高的多药内在抗生素抗性。内在耐药性意味着这些细菌可以耐受大浓度的许多不同类别的抗生素。伯克霍尔德氏菌是对人类非常有用的微生物。它们可以作为生物修复，植物生长促进和害虫生物防治的试剂，但由于担心感染和抗生素耐药性，这些有益的特性实际上仍然无法利用。事实上，一些伯克霍尔德氏菌属物种对人类和家畜特别危险（例如类鼻疽和鼻疽），并且它们被挑选为生物恐怖主义因子，而其他物种（例如B. cenocepacia和B.多噬菌体）在囊性纤维化患者中引起使人衰弱的和通常可传播的肺部感染。伯克氏菌属是巴西甘蔗可培养细菌群落的主要细菌，并且可以通过产生许多不同的抗真菌化合物来控制真菌和感染。我们实验室的研究表明，在广泛使用的昆虫感染模型（Galleria mellonella）中具有高水平抗菌素抗性和增加的细菌毒力的菌株显示出更高的抑制甘蔗病原真菌的能力。这些观察结果表明，抗菌素耐药性和抗真菌剂的生产是相互关联的。我们假设，抗菌素耐药性和抗真菌化合物的生产是协调，使伯克霍尔德氏菌生存在植物中的多微生物植物群的存在下，也捍卫和完成对其他生物体在根际的营养。我们的提案旨在利用这一想法，寻找新的方法来最大限度地发挥伯克霍尔德氏菌在该领域的有益特性（例如抗真菌生产），同时减少临床中的抗菌药物耐药性。我们将结合联合收割机分子微生物学，基因组学和感染模型在植物和昆虫中评估的假设，即抗真菌剂的生产驱动抗生素耐药性的影响生产的分子，提高细菌细胞包膜的不渗透性，从而增加抗生素耐药性，这反过来又增加了细菌的毒力。我们还将利用这些发现开发新的方法来抑制抗生素耐药性和加强害虫生物防治。

The Burkholderiaceae comprises a family of environmental bacteria widespread around the planet, which reside in diverse environments and in association with plants, insects, animals, and humans and also display extraordinarily high multidrug, intrinsic antibiotic resistance. Intrinsic resistance means that these bacteria can tolerate large concentrations of many different classes of antibiotics. Burkholderia are very useful microorganisms for mankind. They can serve as agents for bioremediation, plant growth promotion, and pest biocontrol, but these beneficial properties remain virtually unexploitable because of fear of infection and antibiotic resistance. Indeed, some Burkholderia species are particularly dangerous to humans and domestic animals (e.g. melioidosis and glanders) and they are singled out as bioterrorism agents, while others (e.g. B. cenocepacia and B. multivorans) cause debilitating and often transmissible lung infections in cystic fibrosis patients. Burkholderia spp. is a main bacterium of the sugarcane cultivable bacterial community in Brazil, and can control fungal and infections by producing many different antifungal compounds. Research in our laboratories show that strains with high-level antimicrobial resistance and increased bacterial virulence in a widely used insect infection model (Galleria mellonella) display higher capacity to inhibit sugarcane pathogenic fungi. These observations suggest that antimicrobial resistance and antifungal production are interrelated. We hypothesise that antimicrobial resistance and antifungal compound production are coordinated to allow Burkholderia survival in the presence of a polymicrobial flora in the plants and also to defend and complete for nutrients against other organisms in the rhizosphere. Our proposal aims to exploit this idea to find new ways to maximise the beneficial properties of Burkholderia for use in the field (e.g. antifungal production) while reducing antimicrobial resistance in the clinic. We will combine molecular microbiology, genomics, and infection models in plants and insects to assess the hypothesis that antifungal production drives antimicrobial resistance by influencing the production of molecules that enhance bacterial cell envelope impermeability resulting in increased antibiotic resistance, which in turn increases bacterial virulence. We will also exploit these findings to develop novel ways to inhibit antimicrobial resistance and enhance pest biocontrol.