Abstract

Antibiotic biosynthesis by microorganisms is commonly regulated through autoinduction, which allows producers to quickly amplify the production of antibiotics in response to environmental cues. Antibiotic autoinduction generally involves one pathway-specific transcriptional regulator that perceives an antibiotic as a signal and then directly stimulates transcription of the antibiotic biosynthesis genes. Pyoluteorin is an autoregulated antibiotic produced by some Pseudomonas spp. including the soil bacterium Pseudomonas protegens Pf-5. In this study, we show that PltR, a known pathway-specific transcriptional activator of pyoluteorin biosynthesis genes, is necessary but not sufficient for pyoluteorin autoinduction in Pf-5. We found that pyoluteorin is perceived as an inducer by PltZ, a second pathway-specific transcriptional regulator that directly represses the expression of genes encoding a transporter in the pyoluteorin gene cluster. Mutation of pltZ abolished the autoinducing effect of pyoluteorin on the transcription of pyoluteorin biosynthesis genes. Overall, our results support an alternative mechanism of antibiotic autoinduction by which the two pathway-specific transcriptional regulators PltR and PltZ coordinate the autoinduction of pyoluteorin in Pf-5. Possible mechanisms by which PltR and PltZ mediate the autoinduction of pyoluteorin are discussed.

Highlights

  • Autoinduction, called positive feedback regulation, is commonly used by bacteria to induce phenotypes required to respond promptly to a particular environmental condition [1,2,3]

  • This study focuses on the autoinduction of pyoluteorin, a broad-spectrum antibiotic

  • This study focuses on the autoinduction of pyoluteorin, a broad-spectrum antibiotic produced certain strains strains of ofPseudomonas

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Summary

Introduction

Autoinduction, called positive feedback regulation, is commonly used by bacteria to induce phenotypes required to respond promptly to a particular environmental condition [1,2,3]. The best-documented mechanism is the autoinduction of N-acyl-homoserine lactones, known as quorum sensing signal molecules, which regulate cell-to-cell communication in many bacteria. In addition to the quorum sensing signal molecules, production of many antibiotics is controlled by autoinduction [5,6,7,8,9,10,11,12,13,14,15]. Antibiotics can accumulate rapidly, allowing producers to respond promptly to competition with other microorganisms or predators [7]. Some antibiotics, such as 2,4-diacetylphloroglucinol [16]

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