Small molecule produced by interferes with ubiquinone biosynthesis in Gram-negative bacteria.

Unlabelled: We report the identification of 3,6-dihydroxy-1,2-benzisoxazole (DHB) in a screen of and , whose symbiotic relationship with eukaryotic nematodes favors secondary metabolites that meet several requirements matching those for clinically useful antibiotics. DHB is produced by and is selective against the Gram-negative species and . It is inactive against anaerobic gut bacteria and nontoxic to human cells.

Computational identification of a systemic antibiotic for gram-negative bacteria.

Discovery of antibiotics acting against Gram-negative species is uniquely challenging due to their restrictive penetration barrier. BamA, which inserts proteins into the outer membrane, is an attractive target due to its surface location. Darobactins produced by Photorhabdus, a nematode gut microbiome symbiont, target BamA.

Evybactin is a DNA gyrase inhibitor that selectively kills Mycobacterium tuberculosis.

The antimicrobial resistance crisis requires the introduction of novel antibiotics. The use of conventional broad-spectrum compounds selects for resistance in off-target pathogens and harms the microbiome. This is especially true for Mycobacterium tuberculosis, where treatment requires a 6-month course of antibiotics.

A Silent Operon of Photorhabdus luminescens Encodes a Prodrug Mimic of GTP.

With the overmining of actinomycetes for compounds acting against Gram-negative pathogens, recent efforts to discover novel antibiotics have been focused on other groups of bacteria. Teixobactin, the first antibiotic without detectable resistance that binds lipid II, comes from an uncultured , a betaproteobacterium; odilorhabdins, from , are broad-spectrum inhibitors of protein synthesis, and darobactins from target BamA, the essential chaperone of the outer membrane of Gram-negative bacteria. and are symbionts of the nematode gut microbiome and attractive producers of secondary metabolites.

Pulse Dosing of Antibiotic Enhances Killing of a Biofilm.

Biofilms are highly tolerant to antibiotics and underlie the recalcitrance of many chronic infections. We demonstrate that mature biofilms can be substantially sensitized to the treatment by pulse dosing of an antibiotic - in this case, oxacillin. Pulse (periodic) dosing was compared to continuous application of antibiotic and was studied in a novel flow system which allowed for robust biofilm growth and tractable pharmacokinetics of dosing regimens.