Special Issue "Contexts of Biosynthesis and Functions of the Antibiotics for the Producing Bacteria"

A special issue of Antibiotics (ISSN 2079-6382).

Deadline for manuscript submissions: closed (30 April 2020).

Special Issue Editor

Dr. Marie-Joëlle Virolle
E-Mail Website
Guest Editor
Department of Microbiology, Institute of Integrative Biology of the Cell (I2BC), UMR 9198 CNRS, University Paris Saclay, 91190 Gif sur Yvette, France
Interests: regulation of antibiotic biosynthesis; energetic metabolism; function of antibiotics for the producing bacteria; streptomyces
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

Antibiotics are often seen as weapons conferring a selective advantage to their producers in a given ecological niche. This prevalent view has prevented the legitimate questioning of the function of the produced antibiotics for the producing bacteria. Therefore, this Special Issue constitutes an attempt to relate the context of antibiotic production to the function of these molecules for its producer, in the specific context of their production. A better understanding of such links is expected to lead to original strategies to enhance the expression of the numerous cryptic pathways present in the genome of the producing bacteria. In consequence, any manuscripts concerning the conditions of antibiotics production and their signaling, the function of the antibiotics produced in a specific environmental/physiological context as well as the reporting of original strategies of “decryptification” of silent pathways are welcome.

  1. Conditions of antibiotic production and their signaling;
  2. Different classes of antibiotics, their molecular targets, and their role in the physiology of the bacteria;
  3. Antibiotics as an adaptive response to specific stresses;
  4. Original “decryptification” strategies.

This Special Issue seeks manuscript submissions that will expand and renew our understanding of the triggering of antibiotic biosynthesis by nutritional limitation (crowding/quorum sensing, energetic stress, etc.), the role of antibiotics in programmed cell death, response to oxidative stress, and regulation of energetic metabolism, including the control of respiration and well known inhibition of ATP consuming anabolic processes.

Dr. Marie-Joëlle Virolle
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibiotics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Antibiotics
  • Signaling molecules
  • Regulation
  • Energetic metabolism
  • Oxydative stress
  • Cryptic pathways

Published Papers (6 papers)

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Article
Prodiginines Postpone the Onset of Sporulation in Streptomyces coelicolor
Antibiotics 2020, 9(12), 847; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9120847 - 26 Nov 2020
Cited by 2 | Viewed by 550
Abstract
Bioactive natural products are typically secreted by the producer strain. Besides that, this allows the targeting of competitors, also filling a protective role, reducing the chance of self-killing. Surprisingly, DNA-degrading and membrane damaging prodiginines (PdGs) are only produced intracellularly, and are required for [...] Read more.
Bioactive natural products are typically secreted by the producer strain. Besides that, this allows the targeting of competitors, also filling a protective role, reducing the chance of self-killing. Surprisingly, DNA-degrading and membrane damaging prodiginines (PdGs) are only produced intracellularly, and are required for the onset of the second round of programmed cell death (PCD) in Streptomyces coelicolor. In this work, we investigated the influence of PdGs on the timing of the morphological differentiation of S. coelicolor. The deletion of the transcriptional activator gene redD that activates the red cluster for PdGs or nutrient-mediated reduction of PdG synthesis both resulted in the precocious appearance of mature spore chains. Transcriptional analysis revealed an accelerated expression of key developmental genes in the redD null mutant, including bldN for the developmental σ factor BldN which is essential for aerial mycelium formation. In contrast, PdG overproduction due to the enhanced copy number of redD resulted in a delay or block in sporulation. In addition, confocal fluorescence microscopy revealed that the earliest aerial hyphae do not produce PdGs. This suggests that filaments that eventually differentiate into spore chains and are hence required for survival of the colony, are excluded from the second round of PCD induced by PdGs. We propose that one of the roles of PdGs would be to delay the entrance of S. coelicolor into the dormancy state (sporulation) by inducing the leakage of the intracellular content of dying filaments thereby providing nutrients for the survivors. Full article
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Article
The Onset of Tacrolimus Biosynthesis in Streptomyces tsukubaensis Is Dependent on the Intracellular Redox Status
Antibiotics 2020, 9(10), 703; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9100703 - 15 Oct 2020
Viewed by 897
Abstract
The oxidative stress response is a key mechanism that microorganisms have to adapt to changeling environmental conditions. Adaptation is achieved by a fine-tuned molecular response that extends its influence to primary and secondary metabolism. In the past, the role of the intracellular redox [...] Read more.
The oxidative stress response is a key mechanism that microorganisms have to adapt to changeling environmental conditions. Adaptation is achieved by a fine-tuned molecular response that extends its influence to primary and secondary metabolism. In the past, the role of the intracellular redox status in the biosynthesis of tacrolimus in Streptomyces tsukubaensis has been briefly acknowledged. Here, we investigate the impact of the oxidative stress response on tacrolimus biosynthesis in S. tsukubaensis. Physiological characterization of S. tsukubaensis showed that the onset of tacrolimus biosynthesis coincided with the induction of catalase activity. In addition, tacrolimus displays antioxidant properties and thus a controlled redox environment would be beneficial for its biosynthesis. In addition, S. tsukubaensisahpC strain, a strain defective in the H2O2-scavenging enzyme AhpC, showed increased production of tacrolimus. Proteomic and transcriptomic studies revealed that the tacrolimus over-production phenotype was correlated with a metabolic rewiring leading to increased availability of tacrolimus biosynthetic precursors. Altogether, our results suggest that the carbon source, mainly used for cell growth, can trigger the production of tacrolimus by modulating the oxidative metabolism to favour a low oxidizing intracellular environment and redirecting the metabolic flux towards the increase availability of biosynthetic precursors. Full article
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Article
Negative Correlation between Lipid Content and Antibiotic Activity in Streptomyces: General Rule and Exceptions
Antibiotics 2020, 9(6), 280; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9060280 - 26 May 2020
Cited by 2 | Viewed by 1133
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 [...] Read more.
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. Full article
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Article
Mining the Biosynthetic Potential for Specialized Metabolism of a Streptomyces Soil Community
Antibiotics 2020, 9(5), 271; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9050271 - 23 May 2020
Cited by 10 | Viewed by 1650
Abstract
The diversity and distribution of specialized metabolite gene clusters within a community of bacteria living in the same soil habitat are poorly documented. Here we analyzed the genomes of 8 Streptomyces isolated at micro-scale from a forest soil that belong to the same [...] Read more.
The diversity and distribution of specialized metabolite gene clusters within a community of bacteria living in the same soil habitat are poorly documented. Here we analyzed the genomes of 8 Streptomyces isolated at micro-scale from a forest soil that belong to the same species or to different species. The results reveal high levels of diversity, with a total of 261 biosynthesis gene clusters (BGCs) encoding metabolites such as terpenes, polyketides (PKs), non-ribosomal peptides (NRPs) and ribosomally synthesized and post-translationally modified peptides (RiPPs) with potential bioactivities. A significant part of these BGCs (n = 53) were unique to only one strain when only 5 were common to all strains. The metabolites belong to very diverse chemical families and revealed that a large diversity of metabolites can potentially be produced in the community. Although that analysis of the global metabolome using GC-MS revealed that most of the metabolites were shared between the strains, they exhibited a specific metabolic pattern. We also observed that the presence of these accessory pathways might result from frequent loss and gain of genes (horizontal transfer), showing that the potential of metabolite production is a dynamic phenomenon in the community. Sampling Streptomyces at the community level constitutes a good frame to discover new biosynthetic pathways and it appears as a promising reservoir for the discovery of new bioactive compounds. Full article
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Article
Marine Actinobacteria: Screening for Predation Leads to the Discovery of Potential New Drugs against Multidrug-Resistant Bacteria
Antibiotics 2020, 9(2), 91; https://doi.org/10.3390/antibiotics9020091 - 19 Feb 2020
Cited by 6 | Viewed by 1762
Abstract
Predatory bacteria constitute a heterogeneous group of prokaryotes able to lyse and feed on the cellular constituents of other bacteria in conditions of nutrient scarcity. In this study, we describe the isolation of Actinobacteria predator of other bacteria from the marine water of [...] Read more.
Predatory bacteria constitute a heterogeneous group of prokaryotes able to lyse and feed on the cellular constituents of other bacteria in conditions of nutrient scarcity. In this study, we describe the isolation of Actinobacteria predator of other bacteria from the marine water of the Moroccan Atlantic coast. Only 4 Actinobacteria isolates showing strong predation capability against native or multidrug-resistant Gram-positive or Gram-negative bacteria were identified among 142 isolated potential predatory bacteria. These actinobacterial predators were shown to belong to the Streptomyces genus and to inhibit the growth of various native or multidrug-resistant micro-organisms, including Micrococcus luteus, Staphylococcus aureus (native and methicillin-resistant), and Escherichia coli (native and ampicillin-resistant). Even if no clear correlation could be established between the antibacterial activities of the selected predator Actinobacteria and their predatory activity, we cannot exclude that some specific bio-active secondary metabolites were produced in this context and contributed to the killing and lysis of the bacteria. Indeed, the co-cultivation of Actinobacteria with other bacteria is known to lead to the production of compounds that are not produced in monoculture. Furthermore, the production of specific antibiotics is linked to the composition of the growth media that, in our co-culture conditions, exclusively consisted of the components of the prey living cells. Interestingly, our strategy led to the isolation of bacteria with interesting inhibitory activity against methicillin-resistant S. aureus (MRSA) as well as against Gram-negative bacteria. Full article
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Concept Paper
A Challenging View: Antibiotics Play a Role in the Regulation of the Energetic Metabolism of the Producing Bacteria
Antibiotics 2020, 9(2), 83; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9020083 - 13 Feb 2020
Cited by 10 | Viewed by 1338
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 [...] Read more.
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. Full article
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