Published Paper Details:

Planctomycetes are a group of Gram-negative bacteria that have several peculiar features: they have compartmentalised cytoplasm, they divide without using FtsZ and they produce structurally diverse secondary metabolites with antimicrobial activity. Although they are widely distributed in the environment and are increasingly finding their way into the list of biosynthetic gene clusters, very little research has been conducted systematically for their conserved enzymatic targets as potential targets for antibacterial intervention. To assess binding interactions of eight clinically relevant antibiotics with a homology-modelled UDP-N-acetylglucosamine enolpyruvyl transferase target from the well characterised model planctomycete Rhodopirellula baltica, the present study uses an in silico molecular docking approach. The target enzyme 3D structure has been modeled using SWISS-MODEL and checked by the Ramachandran analysis. Antibiotic ligands, including rifampicin, ciprofloxacin, erythromycin, tetracycline, chloramphenicol, streptomycin, ampicillin and vancomycin, were retrieved from the PubChem database, energy-minimised, and docked into the predicted active site using AutoDock Vina. The contacts of active site residues and hydrogen bonding interactions were systematically analysed and binding affinities were calculated. The most bound ligand was rifampicin with six hydrogen-bond interactions with Ser142, Lys87, Asp231, Arg155, Gln45 and Tyr89 with -10.4 kcal/mol binding affinity, while erythromycin and ciprofloxacin had binding affinities of -9.6 and -9.2 kcal/mol, respectively. The affinity of aminoglycosides and beta-lactams was comparatively weak, which is also consistent with the previously reported resistance profiles of marine Planctomycetes. The study offers a structural explanation for the sensitivity of Planctomycetes to different classes of antibiotics and shows that the MurA-like enzyme is a potential in silico target for narrow-spectrum antibiotics discovery targeted against this phylum.