Antibiotics and Bacterial Metabolism

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

Deadline for manuscript submissions: closed (28 February 2023) | Viewed by 8870

Special Issue Editor

Department of Biology, University of Florence, Via Madonna del Piano 6, 50019 Sesto Fiorentino (FI), Italy
Interests: antibiotic resistance; Burkholderia; efflux pumps; quorum sensing; multipartite genomes
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

A close link between antibiotic efficacy and bacterial metabolism has emerged in recent years. Indeed, currently used antibiotics target a narrow spectrum of macromolecular biosynthetic processes, also perturbing bacterial metabolism and contributing to cell death. Furthermore, it is becoming more and more evident that the metabolic state of bacteria also influences their susceptibility to antibiotics. In particular, cells with a reduced metabolism (for example, during the stationary phase of growth, or persisters or cells embedded in biofilm) show higher resistance to antibiotic action. Consequently, antibiotic efficacy could be enhanced by altering the metabolic state of bacteria.

This Special Issue welcomes submissions from different research fields that deepen the relationship between bacterial metabolism and antibiotic efficacy, to find new ways to overcome the problem of antibiotic resistance.

Dr. Elena Perrin
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 submissions that pass pre-check are 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 2900 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

  • bacterial metabolism
  • antibiotic resistance
  • biofilm
  • persisters
  • metabolic state of cells
  • stationary phase
  • bacteriostatic and bactericidal antibiotics

Published Papers (5 papers)

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Research

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11 pages, 1860 KiB  
Article
Employing Genome Mining to Unveil a Potential Contribution of Endophytic Bacteria to Antimicrobial Compounds in the Origanum vulgare L. Essential Oil
Antibiotics 2023, 12(7), 1179; https://doi.org/10.3390/antibiotics12071179 - 12 Jul 2023
Cited by 1 | Viewed by 933
Abstract
Essential oils (EOs) from medicinal plants have long been used in traditional medicine for their widely known antimicrobial properties and represent a promising reservoir of bioactive compounds against multidrug-resistant pathogens. Endophytes may contribute to the yield and composition of EOs, representing a useful [...] Read more.
Essential oils (EOs) from medicinal plants have long been used in traditional medicine for their widely known antimicrobial properties and represent a promising reservoir of bioactive compounds against multidrug-resistant pathogens. Endophytes may contribute to the yield and composition of EOs, representing a useful tool for biotechnological applications. In this work, we investigated the genomic basis of this potential contribution. The annotated genomes of four endophytic strains isolated from Origanum vulgare L. were used to obtain KEGG ortholog codes, which were used for the annotation of different pathways in KEGG, and to evaluate whether endophytes might harbor the (complete) gene sets for terpene and/or plant hormone biosynthesis. All strains possessed ortholog genes for the mevalonate-independent pathway (MEP/DOXP), allowing for the production of isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) precursors. Ortholog genes for the next steps in terpenoid biosynthesis were scarce. All the strains possess potential plant growth promotion (PGP) ability, as shown by the presence of orthologous genes involved in the biosynthesis of indoleacetic acid. The main contribution of endophytes to the yield and composition of O. vulgare EO very likely resides in their PGP activities and in the biosynthesis of precursors of bioactive compounds. Full article
(This article belongs to the Special Issue Antibiotics and Bacterial Metabolism)
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15 pages, 1967 KiB  
Article
DXP Synthase Function in a Bacterial Metabolic Adaptation and Implications for Antibacterial Strategies
Antibiotics 2023, 12(4), 692; https://doi.org/10.3390/antibiotics12040692 - 01 Apr 2023
Cited by 2 | Viewed by 2365
Abstract
Pathogenic bacteria possess a remarkable ability to adapt to fluctuating host environments and cause infection. Disturbing bacterial central metabolism through inhibition of 1-deoxy-d-xylulose 5-phosphate synthase (DXPS) has the potential to hinder bacterial adaptation, representing a new antibacterial strategy. DXPS functions at [...] Read more.
Pathogenic bacteria possess a remarkable ability to adapt to fluctuating host environments and cause infection. Disturbing bacterial central metabolism through inhibition of 1-deoxy-d-xylulose 5-phosphate synthase (DXPS) has the potential to hinder bacterial adaptation, representing a new antibacterial strategy. DXPS functions at a critical metabolic branchpoint to produce the metabolite DXP, a precursor to pyridoxal-5-phosphate (PLP), thiamin diphosphate (ThDP) and isoprenoids presumed essential for metabolic adaptation in nutrient-limited host environments. However, specific roles of DXPS in bacterial adaptations that rely on vitamins or isoprenoids have not been studied. Here we investigate DXPS function in an adaptation of uropathogenic E. coli (UPEC) to d-serine (d-Ser), a bacteriostatic host metabolite that is present at high concentrations in the urinary tract. UPEC adapt to d-Ser by producing a PLP-dependent deaminase, DsdA, that converts d-Ser to pyruvate, pointing to a role for DXPS-dependent PLP synthesis in this adaptation. Using a DXPS-selective probe, butyl acetylphosphonate (BAP), and leveraging the toxic effects of d-Ser, we reveal a link between DXPS activity and d-Ser catabolism. We find that UPEC are sensitized to d-Ser and produce sustained higher levels of DsdA to catabolize d-Ser in the presence of BAP. In addition, BAP activity in the presence of d-Ser is suppressed by β-alanine, the product of aspartate decarboxylase PanD targeted by d-Ser. This BAP-dependent sensitivity to d-Ser marks a metabolic vulnerability that can be exploited to design combination therapies. As a starting point, we show that combining inhibitors of DXPS and CoA biosynthesis displays synergy against UPEC grown in urine where there is increased dependence on the TCA cycle and gluconeogenesis from amino acids. Thus, this study provides the first evidence for a DXPS-dependent metabolic adaptation in a bacterial pathogen and demonstrates how this might be leveraged for development of antibacterial strategies against clinically relevant pathogens. Full article
(This article belongs to the Special Issue Antibiotics and Bacterial Metabolism)
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14 pages, 2726 KiB  
Article
Bactericidal and Anti-Biofilm Activity of the FtsZ Inhibitor C109 against Acinetobacter baumannii
Antibiotics 2022, 11(11), 1571; https://doi.org/10.3390/antibiotics11111571 - 08 Nov 2022
Cited by 1 | Viewed by 1458
Abstract
In the last few years, Acinetobacter baumannii has ranked as a number one priority due to its Multi Drug Resistant phenotype. The different metabolic states, such as the one adopted when growing as biofilm, help the bacterium to resist a wide variety of [...] Read more.
In the last few years, Acinetobacter baumannii has ranked as a number one priority due to its Multi Drug Resistant phenotype. The different metabolic states, such as the one adopted when growing as biofilm, help the bacterium to resist a wide variety of compounds, placing the discovery of new molecules able to counteract this pathogen as a topic of utmost importance. In this context, bacterial cell division machinery and the conserved protein FtsZ are considered very interesting cellular targets. The benzothiadiazole compound C109 is able to inhibit bacterial growth and to block FtsZ GTPase and polymerization activities in Burkholderia cenocepacia, Pseudomonas aeruginosa, and Staphylococcus aureus. In this work, the activity of C109 was tested against a panel of antibiotic sensitive and resistant A. baumannii strains. Its ability to inhibit biofilm formation was explored, together with its activity against the A. baumannii FtsZ purified protein. Our results indicated that C109 has good MIC values against A. baumannii clinical isolates. Moreover, its antibiofilm activity makes it an interesting alternative treatment, effective against diverse metabolic states. Finally, its activity was confirmed against A. baumannii FtsZ. Full article
(This article belongs to the Special Issue Antibiotics and Bacterial Metabolism)
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Review

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19 pages, 1169 KiB  
Review
Understanding Antimicrobial Resistance Using Genome-Scale Metabolic Modeling
Antibiotics 2023, 12(5), 896; https://doi.org/10.3390/antibiotics12050896 - 11 May 2023
Cited by 1 | Viewed by 1496
Abstract
The urgent necessity to fight antimicrobial resistance is universally recognized. In the search of new targets and strategies to face this global challenge, a promising approach resides in the study of the cellular response to antimicrobial exposure and on the impact of global [...] Read more.
The urgent necessity to fight antimicrobial resistance is universally recognized. In the search of new targets and strategies to face this global challenge, a promising approach resides in the study of the cellular response to antimicrobial exposure and on the impact of global cellular reprogramming on antimicrobial drugs’ efficacy. The metabolic state of microbial cells has been shown to undergo several antimicrobial-induced modifications and, at the same time, to be a good predictor of the outcome of an antimicrobial treatment. Metabolism is a promising reservoir of potential drug targets/adjuvants that has not been fully exploited to date. One of the main problems in unraveling the metabolic response of cells to the environment resides in the complexity of such metabolic networks. To solve this problem, modeling approaches have been developed, and they are progressively gaining in popularity due to the huge availability of genomic information and the ease at which a genome sequence can be converted into models to run basic phenotype predictions. Here, we review the use of computational modeling to study the relationship between microbial metabolism and antimicrobials and the recent advances in the application of genome-scale metabolic modeling to the study of microbial responses to antimicrobial exposure. Full article
(This article belongs to the Special Issue Antibiotics and Bacterial Metabolism)
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Other

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11 pages, 1509 KiB  
Brief Report
Streptozotocin-Induced Hyperglycemia Is Associated with Unique Microbiome Metabolomic Signatures in Response to Ciprofloxacin Treatment
Antibiotics 2022, 11(5), 585; https://doi.org/10.3390/antibiotics11050585 - 27 Apr 2022
Viewed by 1484
Abstract
It is well recognized that the microbiome plays key roles in human health, and that damage to this system by, for example, antibiotic administration has detrimental effects. With this, there is collective recognition that off-target antibiotic susceptibility within the microbiome is a particularly [...] Read more.
It is well recognized that the microbiome plays key roles in human health, and that damage to this system by, for example, antibiotic administration has detrimental effects. With this, there is collective recognition that off-target antibiotic susceptibility within the microbiome is a particularly troublesome side effect that has serious impacts on host well-being. Thus, a pressing area of research is the characterization of antibiotic susceptibility determinants within the microbiome, as understanding these mechanisms may inform the development of microbiome-protective therapeutic strategies. In particular, metabolic environment is known to play a key role in the different responses of this microbial community to antibiotics. Here, we explore the role of host dysglycemia on ciprofloxacin susceptibility in the murine cecum. We used a combination of 16S rRNA sequencing and untargeted metabolomics to characterize changes in both microbiome taxonomy and environment. We found that dysglycemia minimally impacted ciprofloxacin-associated changes in microbiome structure. However, from a metabolic perspective, host hyperglycemia was associated with significant changes in respiration, central carbon metabolism, and nucleotide synthesis-related metabolites. Together, these data suggest that host glycemia may influence microbiome function during antibiotic challenge. Full article
(This article belongs to the Special Issue Antibiotics and Bacterial Metabolism)
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