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Drug Treatment for Bacterial Infections

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pharmacology".

Deadline for manuscript submissions: 20 November 2024 | Viewed by 4151

Special Issue Editor


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Guest Editor
Department of Organic Chemistry, Faculty of Chemistry, University of Gdańsk, Gdańsk, Poland
Interests: carbohydrates; synthesis and analysis of sugar derivatives; vancomycin and its derivatives; sugar hydrazides; cationic sugar compounds; biological activity of sugar derivatives

Special Issue Information

Dear Colleagues,

Bacterial infections, next to viral and fungal infections, are a major threat, especially to human health. Thanks to their ability to mutate, they can quickly create new strains that are resistant to the antibiotics used, which is a significant challenge in the treatment of infections caused by them. Pharmacological treatment of bacterial infections therefore requires the right approach. On the one hand, drug therapy should be conducted responsibly to reduce the risk of drug resistance. On the other hand, it is still necessary to search for new substances that will prove to be more effective and less toxic than the currently used antibiotics. Interesting results in the treatment of bacterial infections are also brought by the use of combination drugs containing more than one active substance.

The possibility of using targeted therapy to treat inflammatory foci is extremely interesting. New forms of drugs that allow the release of the drug substance at the site of infection would allow for a reduction in the dose of the drug and its more effective action.

All new research and review articles on drug therapy for bacterial infections, from new uses of approved drugs, to new drug substances and combination drugs, and further to new drug formulations, are welcome in this Special Issue.

Prof. Dr. Janusz Madaj
Guest Editor

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Keywords

  • bacterial infection
  • antibiotic-resistant bacteria
  • new agents in the treatment of bacterial infections
  • optimization of the use of already registered drugs
  • single antibacterial agents
  • combined antibacterial agents
  • new drug forms

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Published Papers (4 papers)

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Research

19 pages, 6356 KiB  
Article
Acidocin A and Acidocin 8912 Belong to a Distinct Subfamily of Class II Bacteriocins with a Broad Spectrum of Antimicrobial Activity
by Daria V. Antoshina, Sergey V. Balandin, Ekaterina I. Finkina, Ivan V. Bogdanov, Sofia I. Eremchuk, Daria V. Kononova, Alena A. Kovrizhnykh and Tatiana V. Ovchinnikova
Int. J. Mol. Sci. 2024, 25(18), 10059; https://doi.org/10.3390/ijms251810059 - 19 Sep 2024
Cited by 1 | Viewed by 610
Abstract
Within class II bacteriocins, we assume the presence of a separate subfamily of antimicrobial peptides possessing a broad spectrum of antimicrobial activity. Although these peptides are structurally related to the subclass IIa (pediocin-like) bacteriocins, they have significant differences in biological activities and, probably, [...] Read more.
Within class II bacteriocins, we assume the presence of a separate subfamily of antimicrobial peptides possessing a broad spectrum of antimicrobial activity. Although these peptides are structurally related to the subclass IIa (pediocin-like) bacteriocins, they have significant differences in biological activities and, probably, a mechanism of their antimicrobial action. A representative of this subfamily is acidocin A from Lactobacillus acidophilus TK9201. We discovered the similarity between acidocin A and acidocin 8912 from Lactobacillus acidophilus TK8912 when analyzing plasmids from lactic acid bacteria and suggested the presence of a single evolutionary predecessor of these peptides. We obtained the C-terminally extended homolog of acidocin 8912, named acidocin 8912A, a possible intermediate form in the evolution of the former. The study of secondary structures and biological activities of these peptides showed their structural similarity to acidocin A; however, the antimicrobial activities of acidocin 8912 and acidocin 8912A were lower than that of acidocin A. In addition, these peptides demonstrated stronger cytotoxic and membranotropic effects. Building upon what we previously discovered about the immunomodulatory properties of acidocin A, we studied its proteolytic stability under conditions simulating those in the digestive tract and also assessed its ability to permeate intestinal epithelium using the Caco-2 cells monolayer model. In addition, we found a pronounced effect of acidocin A against fungi of the genus Candida, which might also expand the therapeutic potential of this bacterial antimicrobial peptide. Full article
(This article belongs to the Special Issue Drug Treatment for Bacterial Infections)
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18 pages, 3059 KiB  
Article
Exploration of the Graphene Quantum Dots-Blue Light Combination: A Promising Treatment against Bacterial Infection
by Roberto Rosato, Giulia Santarelli, Alberto Augello, Giordano Perini, Marco De Spirito, Maurizio Sanguinetti, Massimiliano Papi and Flavio De Maio
Int. J. Mol. Sci. 2024, 25(15), 8033; https://doi.org/10.3390/ijms25158033 - 23 Jul 2024
Viewed by 953
Abstract
Graphene Quantum Dots (GQDs) have shown the potential for antimicrobial photodynamic treatment, due to their particular physicochemical properties. Here, we investigated the activity of three differently functionalized GQDs—Blue Luminescent GQDs (L-GQDs), Aminated GQDs (NH2-GQDs), and Carboxylated GQDs (COOH-GQDs)—against E. coli. [...] Read more.
Graphene Quantum Dots (GQDs) have shown the potential for antimicrobial photodynamic treatment, due to their particular physicochemical properties. Here, we investigated the activity of three differently functionalized GQDs—Blue Luminescent GQDs (L-GQDs), Aminated GQDs (NH2-GQDs), and Carboxylated GQDs (COOH-GQDs)—against E. coli. GQDs were administrated to bacterial suspensions that were treated with blue light. Antibacterial activity was evaluated by measuring colony forming units (CFUs) and metabolic activities, as well as reactive oxygen species stimulation (ROS). GQD cytotoxicity was then assessed on human colorectal adenocarcinoma cells (Caco-2), before setting in an in vitro infection model. Each GQD exhibits antibacterial activity inducing ROS and impairing bacterial metabolism without significantly affecting cell morphology. GQD activity was dependent on time of exposure to blue light. Finally, GQDs were able to reduce E. coli burden in infected Caco-2 cells, acting not only in the extracellular milieu but perturbating the eukaryotic cell membrane, enhancing antibiotic internalization. Our findings demonstrate that GQDs combined with blue light stimulation, due to photodynamic properties, have a promising antibacterial activity against E. coli. Nevertheless, we explored their action mechanism and toxicity on epithelial cells, fixing and standardizing these infection models. Full article
(This article belongs to the Special Issue Drug Treatment for Bacterial Infections)
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15 pages, 1410 KiB  
Article
Oxolane Ammonium Salts (Muscarine-Like)—Synthesis and Microbiological Activity
by Patrycja Bogdanowicz, Janusz Madaj, Piotr Szweda, Artur Sikorski, Justyna Samaszko-Fiertek and Barbara Dmochowska
Int. J. Mol. Sci. 2024, 25(4), 2368; https://doi.org/10.3390/ijms25042368 - 17 Feb 2024
Viewed by 1004
Abstract
Commercially available 2-deoxy-D-ribose was used to synthesize the appropriate oxolane derivative—(2R,3S)-2-(hydroxymethyl)oxolan-3-ol—by reduction and dehydration/cyclization in an acidic aqueous solution. Its monotosyl derivative, as a result of the quaternization reaction, allowed us to obtain eight new muscarine-type derivatives containing a [...] Read more.
Commercially available 2-deoxy-D-ribose was used to synthesize the appropriate oxolane derivative—(2R,3S)-2-(hydroxymethyl)oxolan-3-ol—by reduction and dehydration/cyclization in an acidic aqueous solution. Its monotosyl derivative, as a result of the quaternization reaction, allowed us to obtain eight new muscarine-type derivatives containing a quaternary nitrogen atom and a hydroxyl group linked to the oxolane ring. Their structure was fully confirmed by the results of NMR, MS and IR analyses. The crystal structure of the pyridinium derivative showed a high similarity of the conformation of the oxolane ring to previously published crystal structures of muscarine. Two reference strains of Gram-negative bacteria (Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853), two reference strains of Gram-positive staphylococci (Staphylococcus aureus ATCC 25923 and Staphylococcus aureus ATCC 29213) and four reference strains of pathogenic yeasts of the genus Candida spp. (Candida albicans SC5314, Candida glabrata DSM 11226, Candida krusei DSM 6128 and Candida parapsilosis DSM 5784) were selected for the evaluation of the antimicrobial potential of the synthesized compounds. The derivative containing the longest (decyl) chain attached to the quaternary nitrogen atom turned out to be the most active. Full article
(This article belongs to the Special Issue Drug Treatment for Bacterial Infections)
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18 pages, 3687 KiB  
Article
Radiosynthesis and Bioevaluation of 99mTc-Labeled Isocyanide Ubiquicidin 29-41 Derivatives as Potential Agents for Bacterial Infection Imaging
by Yuhao Jiang, Peiwen Han, Guangxing Yin, Qianna Wang, Junhong Feng, Qing Ruan, Di Xiao and Junbo Zhang
Int. J. Mol. Sci. 2024, 25(2), 1045; https://doi.org/10.3390/ijms25021045 - 15 Jan 2024
Cited by 3 | Viewed by 1173
Abstract
To develop a novel 99mTc-labeled ubiquicidin 29-41 derivative for bacterial infection single-photon emission computed tomography (SPECT) imaging with improved target-to-nontarget ratio and lower nontarget organ uptake, a series of isocyanide ubiquicidin 29-41 derivatives (CNnUBI 29-41, n = 5–9) with different carbon linkers [...] Read more.
To develop a novel 99mTc-labeled ubiquicidin 29-41 derivative for bacterial infection single-photon emission computed tomography (SPECT) imaging with improved target-to-nontarget ratio and lower nontarget organ uptake, a series of isocyanide ubiquicidin 29-41 derivatives (CNnUBI 29-41, n = 5–9) with different carbon linkers were designed, synthesized and radiolabeled with the [99mTc]Tc(I)+ core, [99mTc][Tc(I)(CO)3(H2O)3]+ core and [99mTc][Tc(V)N]2+ core. All the complexes are hydrophilic, maintain good stability and specifically bind Staphylococcus aureus in vitro. The biodistribution in mice with bacterial infection and sterile inflammation demonstrated that [99mTc]Tc-CN5UBI 29-41 was able to distinguish bacterial infection from sterile inflammation, which had an improved abscess uptake and a greater target-to-nontarget ratio. SPECT imaging study of [99mTc]Tc-CN5UBI 29-41 in bacterial infection mice showed that there was a clear accumulation in the infection site, suggesting that this radiotracer could be a potential radiotracer for bacterial infection imaging. Full article
(This article belongs to the Special Issue Drug Treatment for Bacterial Infections)
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