Dey Ritisha, Valle Domonique Olivia, Chakraborty Abhijit, Mayer Kimberly A, Uppala Jagadeesh Kumar, Chakraborty Anish, Mirza Shama, Skwor Troy, Forst Steven, Dey Madhusudan
Department of Biological Sciences, University of Wisconsin-Milwaukee, Milwaukee, WI, United States.
Center for Cancer Immunotherapy, La Jolla Institute for Immunology, La Jolla, CA, United States.
Front Microbiol. 2025 Mar 12;16:1560663. doi: 10.3389/fmicb.2025.1560663. eCollection 2025.
The decades-long gap in antibiotic discovery has led to a significant health crisis due to antimicrobial resistance (AMR). The bacterial genus , which forms symbiotic relationships with the soil nematode , are known to secrete a variety of antimicrobial compounds with potential effectiveness against AMR. These antimicrobial compounds are primarily bio-synthesized by non-ribosomal peptide synthetases (NRPS) and polyketide synthase (PKS) genes. In this study, we report that produces high levels of antibiotic activity during the stationary phase against diverse bacteria including known antibiotic resistant pathogens. It possesses 17 operons to encode predicted NRPS and PKS enzymes, designated as through . The and operons are predicted to produce the known antibiotics Pax peptide and Fabclavine, respectively. Additionally, the newly identified operons , , , , and consist of single genes, each containing two or more genes. The operon harbors two genes, while the ste7 and ste12 operons contain three genes each. Further, RNA-seq analysis showed that that encodes a quorum sensing autoinducer-2 (AI-2) thiolase was expressed at high levels during stationary phase. These findings provide evidence that uses quorum sensing (QS) to synchronize the expression of multiple NRPS and PKS enzymes responsible for synthesizing various antimicrobial compounds. This study underscores the potential to leverage these regulatory insights for maximizing commercial applications of novel antibiotics combating AMR, as well as broader industrial uses.
由于抗菌药物耐药性（AMR），长达数十年的抗生素发现差距已导致严重的健康危机。已知与土壤线虫形成共生关系的细菌属会分泌多种对抗AMR具有潜在效力的抗菌化合物。这些抗菌化合物主要由非核糖体肽合成酶（NRPS）和聚酮化合物合成酶（PKS）基因进行生物合成。在本研究中，我们报告称，[细菌名称]在稳定期对包括已知抗生素耐药病原体在内的多种细菌产生高水平的抗生素活性。它拥有17个操纵子来编码预测的NRPS和PKS酶，分别命名为[操纵子名称1]至[操纵子名称17]。预计[操纵子名称1]和[操纵子名称2]操纵子分别产生已知抗生素Pax肽和法克拉维因。此外，新鉴定的操纵子[操纵子名称3]、[操纵子名称4]、[操纵子名称5]、[操纵子名称6]和[操纵子名称7]由单个基因组成，每个基因包含两个或更多[特定基因名称]基因。[操纵子名称8]操纵子含有两个[特定基因名称]基因，而ste7和ste12操纵子各含有三个[特定基因名称]基因。此外，RNA测序分析表明，编码群体感应自诱导物-2（AI-2）硫解酶的[基因名称]在稳定期高水平表达。这些发现提供了证据，表明[细菌名称]利用群体感应（QS）来同步负责合成各种抗菌化合物的多种NRPS和PKS酶的表达。本研究强调了利用这些调控见解来最大化对抗AMR的新型抗生素的商业应用以及更广泛的工业用途的潜力。
