Abstract
Antibiotics are often considered as weapons conferring a competitive advantage to their producers in their ecological niche. However, since these molecules are produced in specific environmental conditions, notably phosphate limitation that triggers a specific metabolic state, they are likely to play important roles in the physiology of the producing bacteria that have been overlooked. Our recent experimental data as well as careful analysis of the scientific literature led us to propose that, in conditions of moderate to severe phosphate limitation—conditions known to generate energetic stress—antibiotics play crucial roles in the regulation of the energetic metabolism of the producing bacteria. A novel classification of antibiotics into types I, II, and III, based on the nature of the targets of these molecules and on their impact on the cellular physiology, is proposed. Type I antibiotics are known to target cellular membranes, inducing energy spilling and cell lysis of a fraction of the population to provide nutrients, and especially phosphate, to the surviving population. Type II antibiotics inhibit respiration through different strategies, to reduce ATP generation in conditions of low phosphate availability. Lastly, Type III antibiotics that are known to inhibit ATP consuming anabolic processes contribute to ATP saving in conditions of phosphate starvation.
Highlights
The Streptomyces genus is the most prolific producer of bioactive molecules that include numerous substances useful to human, animal, and plant health [1]
It has long been known that the biosynthesis of most antibiotics takes place in the period of slow or no growth and that phosphate limitation is a major trigger of antibiotics biosynthesis [5]
One of the major responses to phosphate limitation is the induction of the expression of the two component system (TCS) PhoR/PhoP [7] that positively controls the expression of genes encoding proteins involved in the scavenging and uptake of phosphate (Pi) and negatively controls the expression of genes involved in the assimilation of nitrogen (N) [8,9]
Summary
The Streptomyces genus is the most prolific producer of bioactive molecules that include numerous substances useful to human, animal, and plant health [1]. Some of these molecules have a signaling function and play a role in regulatory cascades leading to pathogenesis [2,3], but most of them have an antibiotic function [4]. The links between a limitation in phosphate and the production of antibiotics remains poorly understood In this Issue, a novel understanding of such links and novel functions of the antibiotics in the physiology of the producer are proposed. These proposals are based on recent experimental data from our group as well as on careful analysis of the abundant literature of the field
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