An inhibitory compound produced by a soil isolate of Rhodococcus has strong activity against the veterinary pathogen R. equi

Complete genome sequencing of dozens of strains of the soil bacterium Rhodococcus has revealed the presence of many cryptic biosynthetic gene clusters, presumably dedicated to the production of small molecules. This has sparked a renewed interest in this underexplored member of the Actinobacteria as...

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Bibliographic Details
Published in:PloS one 2018-12, Vol.13 (12), p.e0209275-e0209275
Main Authors: Ward, Amber L, Reddyvari, Pushpavathi, Borisova, Ralitsa, Shilabin, Abbas G, Lampson, Bert C
Format: Article
Language:English
Subjects:
Actinomycetales Infections - drug therapy
Anti-Bacterial Agents - isolation & purification
Anti-Bacterial Agents - metabolism
Anti-Bacterial Agents - pharmacology
Antibiotics
Atomic properties
Bacteria
Bacterial genetics
Bacterial Proteins - genetics
Bacterial Proteins - isolation & purification
Bacterial Proteins - metabolism
Bacterial Proteins - pharmacology
Bioactive compounds
Biology and Life Sciences
Biosynthesis
Clusters
Culture
DNA Transposable Elements
Gene clusters
Gene sequencing
Genes
Genetic aspects
Genome, Bacterial
Genomes
Gram-negative bacteria
Health sciences
Medicine and Health Sciences
Metabolites
Microbiological synthesis
Mutants
Mutation
Pathogens
Peptides
Polyketide synthase
Research and analysis methods
Rhodococcus
Rhodococcus - drug effects
Rhodococcus - genetics
Rhodococcus - isolation & purification
Rhodococcus - metabolism
Soil
Soil bacteria
Soil microbiology
Soil microorganisms
Veterinary medicine
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Summary:Complete genome sequencing of dozens of strains of the soil bacterium Rhodococcus has revealed the presence of many cryptic biosynthetic gene clusters, presumably dedicated to the production of small molecules. This has sparked a renewed interest in this underexplored member of the Actinobacteria as a potential source of new bioactive compounds. Reported here is the discovery of a potent inhibitory molecule produced by a newly isolated strain of Rhodococcus, strain MTM3W5.2. This small inhibitory molecule shows strong activity against all Rhodococcus species tested, including the veterinary pathogen R. equi, and some closely related genera. It is not active against other Gram positive or Gram negative bacteria. A screen of random transposon mutants identified a gene required to produce this inhibitory compound. This gene is a large multi-domain, type I polyketide synthase that is part of a very large multi-gene biosynthetic gene cluster in the chromosome of strain MTM3W5.2. The high resolution mass spectrum of a major chromatogram peak from a broth culture extract of MTM3W5.2 shows the presence of a compound at m/z 911.5490 atomic mass units. This compound is not detected in the culture extracts from a non-producing mutant strain of MTM3W5.2. A large gene cluster containing at least 14 different type I polyketide synthase genes is proposed to be required to synthesize this antibiotic-like compound.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0209275