Controlling Bacterial Weapons: Biosynthesis and Regulation of Antifungal, Antibacterial and Nematicidal Metabolites in Serratia

M. A. Matilla1, J. E. E. U. Hellberg2, G. P. C. Salmond3, T. Krell1

Author address: 

1EEZ-CSIC, Granada, Spain, 2Univ. of Cambridge, Cambridfe, United Kingdom, 3Univ. of Cambridge, Cambridge, United Kingdom

Abstract: 

The extended use of antibiotics and chemical pesticides has driven the emergency of multidrug resistance microorganisms. As a consequence, great efforts are being made to isolate and develop new broad-spectrum antibiotics. Soil bacteria are a promising source of secondary metabolites, which are mainly synthesized by large multifunctional enzymes known as polyketide synthases (PKSs) and non-ribosomal peptide synthetases (NRPSs). During the screening of a collection of soil and plant-associated bacteria, we found that one of them, the rhizobacterium, Serratia plymuthica A153, showed a broad spectrum of biological activities - including antifungal, anti-nematode, and antibacterial. Using genome sequencing, mutagenesis, chemical analyses and in vivo antagonistic and virulence assays, we identified three secondary metabolites as responsible for the observed bioactivities. Firstly, we isolated and characterized for the first time the PKS gene cluster responsible for the biosynthesis of the antifungal and antioomycete haterumalide, oocydin A. Secondly, we found that A153 produces the hybrid NRPS/PKS antibacterial acetyl-CoA carboxylase inhibitor, andrimid. Finally, we demonstrated that the observed nematicide properties are due to the production of the PKS/NRPS antibiotic, zeamine. Using the nematode worm, Caenorhabditis elegans as a model organism, we showed that early larvae are more sensitive to zeamine. We also investigated the genetic regulation of these three secondary metabolites. Our results showed that the expression of their respective gene clusters is highly controlled at both transcriptional and posttranscriptional levels - highlighting the complexity of the regulatory mechanisms controlling secondary metabolism in this enterobacterium.
2016

abstract No: 

SATURDAY-402

Full conference title: 

ASM Microbe 2016
    • ASM microbe 1st (2016)