The growing threat of antimicrobial resistance necessitates the discovery of novel antibiotics with activity against drug-resistant pathogens. Members of the genus Paenibacillus are a rich source of nonribosomal peptides (NRPs), including well-known antibiotics such as polymyxins, paenibacterin and tridecaptins. Here we use a targeted Mass-QL-based mass spectrometry approach to identify the NRPs produced by a collection of 227 taxonomically diverse plant-associated Paenibacillus strains, providing detailed insights into their NRP-producing potential. Using MassQL to zoom in specifically on NRPs containing basic amino acids, we discovered a novel family of bacitracins, which we designated paenitracins. The paenitracins are the first bacitracin-type peptides reported in Paenibacillus, and are distinguished from canonical bacitracins by three previously unseen amino acid substitutions. The paenitracins exhibit potent activity against Gram-positive pathogens, including vancomycin-resistant Enterococcus faecium E155. Our work provides a novel metabolomics- and genomics-guided workflow for the discovery of bioactive NRPs as a strategy to prioritize natural product chemical space and accelerate antibiotic discovery.

Many antibiotics are ineffective against Gram-negative pathogens such as Pseudomonas aeruginosa because they cannot penetrate the bacterial outer membrane. Here, we show that protein antibiotics calle...

Nature Communications - This study reveals that an outer membrane protein from the predator Bdellovibrio bacteriovorus forms a pentameric assembly that traps a lipid monolayer within. This allows...

Cell division in many archaea requires the coordinated activities of two distinct FtsZ proteins, which are part of the midcell division ring. Here, Liao et al. show that an additional protein, CdpA, o...

The MmpL5/MmpS5 efflux system is crucial for drug extrusion and siderophore export in M. tuberculosis. Here, the authors report its high-resolution cryo-EM structures, revealing a unique trimeric asse...

Diverse bacteria use the high-affinity membrane transport protein PqqU to scavenge the nutrient PQQ from the environment.

Communications Biology - Discovery of a bicyclic peptide inhibitor of cell wall biosynthesis in the Enterobacterales demonstrates applicability of a modified phage display platform to antibiotic...

The mechanisms underlying bacterial chromosome configuration are not fully understood. Here, Spahn et al. show that the Escherichia coli nucleoid adopts a condensed, membrane-proximal configuration du...

The first step of cell division is deforming the planar cell membrane inward towards the cytoplasm. As deforming membranes is energetically costly, biology has developed various protein systems to acc...

Partitioning of FtsN and the septal peptidoglycan synthesis complex between an active synthesis track and an inactive denuded glycan track coordinates opposing peptidoglycan synthesis and degradation ...

UKHSA has published an updated antimicrobial stewardship tool

If successful, it would be the first new class of drug against certain bacteria strains for more than 50 years