Nature. New antibiotics are used to discover insect pathogen nematodes.

According to the information released by the World Health Organization, antibiotic resistance is one of the biggest threats to global health, food safety and development. The effectiveness of antibiotics commonly used in the treatment of infectious diseases is gradually weakening, which makes the treatment of pneumonia, tuberculosis, gonorrhea and Salmonella face crisis [1].at present, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii have developed resistance to most antibiotics, even to all antibiotics in some cases.therefore, the development of new antibiotics targeting these resistant gram-negative pathogens is an urgent problem.gram negative bacteria are common opportunistic pathogens in human body, and they are highly abundant in intestinal microorganisms of entomopathogenic nematodes [3].when nematodes invade insect eggs, they release symbiotic microorganisms, which first paralyze prey with neurotoxins, and then release antibiotics to resist microorganisms in the surrounding environment.the antibiotics released by nematodes are harmless to themselves and can pass through the host eggs, indicating that these antibiotics have low toxicity to themselves and have good pharmacokinetic activities targeting Gram-negative pathogens, which is a potential resource pool for exploring new antibiotics.recently, a team of Professor Kim Lewis from Northeastern University of the United States published an article entitled "a new antibacterial selective kills gram negative pathways" in Nature magazine.in this study, a new antibiotic, darobactin, was screened from Photorhabdus strain. The antibiotic has high bactericidal activity against Gram-negative pathogens and has broad prospects for clinical transformation.Photorhabdus and Xenorhabdus are closely related to gram negative Enterobacteriaceae.firstly, 74 communities of 22 strains of these two strains were used to screen the growth inhibition of E. coli.the results showed that hgb1456 from P. khanii could significantly inhibit the growth of E. coli.mass spectrometry and NMR analysis showed that the active component was darobactin, and genome sequencing analysis showed that darobactin was produced by Dar operon.darobactin has a wide range of bactericidal activity against Gram-negative bacteria, but has low activity against Gram-negative intestinal symbionts including Bacteroides and Gram-positive bacteria [4].subsequently, the outer membrane protein Bama was found to be a binding target of darobactin (Fig. 1).further high-resolution NMR studies showed that darobactin could inhibit Bama and destroy the formation of functional outer membrane structure.finally, the authors confirmed the bactericidal effect of darobactin in vivo by using the septicemia model of mice, indicating that darobactin is a potential antibiotic for the treatment of Gram-negative bacteria.Fig. 1 darobactin inhibits Bama and destroys the outer membrane structure. To sum up, a new antibiotic named darobactin was found in photohabdus, a symbiotic microorganism of entomopathogenic nematodes.this compound can inhibit Bama and destroy the outer membrane structure in vitro and in mouse models, and play an important role in the development of new antibiotics. Tacconilli, e. et al. Discovery, research, and development of new antibiotics: the WHO priority list of antimicrobial resistant bacteria and tuberculosis. Lancet influence dis 18, 318-327 (2018). 2. Payne, D. J., Gwynn, M. n., Holmes, D. J. & Pompliano, D. L. Drugs for bad bugs: confronting the challenges of antibacterial discovery. Nat Rev Drug Discov 6, 29-40 (2007).3. Tambong, J. T. Phylogeny of bacteria isolated from Rhabditis sp. (Nematoda) and identification of novel entomopathogenic Serratia marcescens strains. Curr Microbiol 66, 138-144 (2013).4. Lloyd-Price, J.,Abu-Ali, G. & Huttenhower, C. The healthy human microbiome. Genome Med 8, 51 (2016).