Chromomycin, an antibiotic produced by Streptomyces flaviscleroticus might play a role in the resistance to oxidative stress and is essential for viability in stationary phase

Abstract

Summary The well‐known role of antibiotics in killing sensitive organisms has been challenged by the effects they exert at subinhibitory concentrations. Unfortunately, there are very few published reports on the advantages these molecules may confer to their producers. This study describes the construction of a genetically verified deletion mutant of Streptomyces flaviscleroticus unable to synthesize chromomycin. This mutant was characterized by a rapid loss of viability in stationary phase that was correlated with high oxidative stress and altered antioxidant defences. Altered levels of key metabolites in the mutant signalled a redistribution of the glycolytic flux toward the PPP to generate NADPH to fight oxidative stress as well as reduction of ATP‐phosphofructokinase and Krebs cycle enzymes activities. These changes were correlated with a shift in the preference for carbon utilization from glucose to amino acids. Remarkably, chromomycin at subinhibitory concentration increased longevity of the non‐producer and restored most of the phenotypic features’ characteristic of the wild type strain. Altogether these observations suggest that chromomycin may have antioxidant properties that would explain, at least in part, some of the phenotypes of the mutant. Our observations warrant reconsideration of the secondary metabolite definition and raise the possibility of crucial roles for their producers.

Expression of genes of the Pho regulon is altered in Streptomyces coelicolor

“…S8). Interestingly, some reports in the literature mention that oxidative stress is an important trigger of antibiotic production [93][94][95] and that some antibiotics (for example chromomycin), have anti-oxidant properties 96 and thus constitute an adaptive response to oxidative stress.…”

A Challenging View: Antibiotics Play a Role in the Regulation of the Energetic Metabolism of the Producing Bacteria

“…Some of these antibiotics, including ACT, contain quinone groups that are able to capture electrons [31]. They have thus antioxidant properties, and their biosynthesis could be considered as an adaptive response to oxidative stress (for example, chromomycin [32]). Furthermore, and most importantly, these molecules also have the ability to reduce the electron flow in the respiratory chain, leading to lower efficiency of the latter and thus to a reduction of ATP generation.…”

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

“…Furthermore, to explain the unexpected lower antibiotic activity on glycerol than on glucose, we propose that oxidative stress might be less severe on glycerol than on glucose since the catabolism of glycerol-and more precisely its conversion into dihydroxyacetone by a glycerol dehydrogenase or into glyceraldehyde by a glyceraldehyde reductase-generates more NADPH than the catabolism of glucose [36,37]. NADPH is an indispensable reduced co-factor necessary to combat and thus reduce oxidative stress [38], since some reports in the literature mention that the biosynthesis of specific antibiotics might be triggered by oxidative stress [39][40][41][42][43]. The biosynthesis of such antibiotics is thus expected to be reduced on glycerol.…”