Negative Correlation between Lipid Content and Antibiotic Activity in Streptomyces: General Rule and Exceptions.

Michelle David,Pierre Chaminade,Clara Lejeune,Sonia Abreu,Marie-Joelle Virolle,Annabelle Thibessard,Pierre Leblond

doi:10.3390/antibiotics9060280

Abstract

Streptomycetes are well known antibiotic producers and are among the rare prokaryotes able to store carbon as lipids. Previous comparative studies of the weak antibiotic producer Streptomyces lividans with its ppk mutant and with Streptomyces coelicolor, which both produce antibiotics, suggested the existence of a negative correlation between total lipid content and the ability to produce antibiotics. To determine whether such a negative correlation can be generalized to other Streptomyces species, fifty-four strains were picked randomly and grown on modified R2YE medium, limited in phosphate, with glucose or glycerol as the main carbon source. The total lipid content and antibiotic activity against Micrococcus luteus were assessed for each strain. This study revealed that the ability to accumulate lipids was not evenly distributed among strains and that glycerol was more lipogenic than glucose and had a negative impact on antibiotic biosynthesis. Furthermore, a statistically significant negative Pearson correlation between lipid content and antibiotic activity could be established for most strains, but a few strains escape this general law. These exceptions are likely due to limits and biases linked to the type of test used to determine antibiotic activity, which relies exclusively on Micrococcus luteus sensitivity. They are characterized either by high lipid content and high antibiotic activity or by low lipid content and undetectable antibiotic activity against Micrococcus luteus. Lastly, the comparative genomic analysis of two strains with contrasting lipid content, and both named Streptomyces antibioticus (DSM 41,481 and DSM 40,868, which we found to be phylogenetically related to Streptomyces lavenduligriseus), indicated that some genetic differences in various pathways related to the generation/consumption of acetylCoA could be responsible for such a difference.

Highlights

IntroductionThe Streptomyces genus is a well-known producer of most antibiotics in current use and of a variety of other bioactive molecules useful to human health (e.g., anti-cancer and anti-inflammatory drugs) or agriculture (e.g., fungicides, pesticides, insecticides and herbicides) [1,2,3,4]
The Streptomyces genus is a well-known producer of most antibiotics in current use and of a variety of other bioactive molecules useful to human health or agriculture [1,2,3,4]
We tried to determine whether a statistically significant negative Pearson correlation could be established between total lipid content and antibiotic activity in Streptomyces species, since previous studies suggested that such a correlation might exist [7]

Summary

Introduction

The Streptomyces genus is a well-known producer of most antibiotics in current use and of a variety of other bioactive molecules useful to human health (e.g., anti-cancer and anti-inflammatory drugs) or agriculture (e.g., fungicides, pesticides, insecticides and herbicides) [1,2,3,4]. Streptomyces is one of the rare prokaryotes to have the ability to accumulate storage lipids of the triacylglycerol family when cultivated under nitrogen and/or phosphate limitation [5] S. coelicolor suffers energetic stress since the two component system PhoR/PhoP that positively controls the phosphate supply, necessary for ATP synthesis, is weakly expressed in this strain [9] whereas the ppk mutant suffers energetic stress since its lacks PPK, an important enzyme that regenerates ATP from ADP and polyphosphate [10,11] In these two strains, similar homeostatic processes are triggered to restore their energetic balance [7,9]. The activation of the oxidative metabolism of these strains was shown to be correlated with the production of the antibiotics

Methods

Results

Conclusion