Mechanism of CuO nano-particles on stimulating production of actinorhodin in Streptomyces coelicolor by transcriptional analysis

Xiaomei Liu,Jingchun Tang,Rutao Liu,Lan Wang

doi:10.1038/s41598-019-46833-1

Xiaomei Liu, Jingchun Tang + Show 2 more

Open Access

https://doi.org/10.1038/s41598-019-46833-1

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Journal: Scientific Reports	Publication Date: Aug 2, 2019
Citations: 12	License type: open-access

Affiliation: Nankai University, Shandong University

Abstract

In this research, antibiotic-producing bacteria, Streptomyces coelicolor (S. coelicolor) M145, was exposed to copper oxide (CuO) particles to investigate the effects of nano-particles (NPs) on antibiotic production. Results showed that a higher yield of antibiotics was obtained with smaller particle sizes of CuO NPs. When exposed to 10 mg/L of 40 nm CuO NPs, the maximum amount of actinorhodin (ACT) obtained was 2.6 mg/L after 144 h, which was 2.0-fold greater than that of control. However, the process was inhibited when the concentration of CuO NPs was increased to higher than 20 mg/L. Transcriptome analysis showed that all the genes involved in the ACT cluster were significantly up-regulated after exposure to 10 mg/L NPs, which could be the direct cause of the increase of ACT production. Additionally, some genes related to the generation of acetyl-coA were up-regulated. In this way, CuO NPs led to an increase of secondary metabolites. The mechanism related to these changes indicated that nano-particle‒induced ROS and Cu2+ played synergetic roles in promoting ACT biosynthesis. This is a first report suggesting that CuO NPs had a significant effect on antibiotic production, which will be helpful in understanding the mechanism of antibiotic production in nature.

Highlights

Streptomyces is a gram-positive bacterium, which is widely relevant as it can currently produce two thirds of antibiotics used in clinical settings[1]
The relative abundance of viable bacteria was 84.4% of control (Fig. 1b). This suggested that CuO NPs caused some toxicity to bacteria, they could improve the ability of antibiotic production of individual cells at lower concentrations
When CuO NPs concentration reached 20 mg/L, the ACT yield was 0.76-fold of control at 144 h, while the relative abundance of viable bacteria was 78.9% of control, which meant that with higher concentration of NPs, the ability of antibiotic production of individual cells decreased

Summary

Introduction

Streptomyces is a gram-positive bacterium, which is widely relevant as it can currently produce two thirds of antibiotics used in clinical settings[1]. Antibiotic production of M145 is controlled by many factors, such as transcriptional regulators, proposed coupling of antibiotic synthesis and resistance genes[7], nutritional and metabolic status[8,9], and so on. These regulatory mechanisms are affected by external environment, such as variations in culture conditions and the addition of different factors to the culture medium[10]. Nanoparticles have been widely reported to have toxic effects on microorganisms; there are few reports on whether NPs could affect the secondary metabolites of microbes. The mechanisms behind this phenomenon were investigated by analysing the roles of reactive oxygen species (ROS)

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Results

Conclusion