Antibiotic Adjuvants: An Approach to Overcoming Multi-Drug Resistance and Biofilm Infections

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Antibiofilm Strategies".

Deadline for manuscript submissions: closed (15 August 2024) | Viewed by 6889

Special Issue Editors


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Centro de Química Estrutural, Associação do Instituto Superior Técnico para a Investigação e Desenvolvimento, Lisbon, Portugal
Interests: azamacrocyles; antimicrobials; antitumorals; metallodrugs
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Faculty of Health Sciences, University Fernando Pessoa, Porto, Portugal
Interests: bioactive compounds; antitumor compounds; antimicrobial compounds; immunomodulation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The incidence of infectious diseases caused by multi-drug-resistant pathogens has been increasing over the last few decades. These microorganisms are difficult to eradicate and are associated with worst outcomes than those caused by the respective susceptible strains. In addition, biofilm-associated microorganisms have shown a much higher resistance to antibiotics than planktonic microorganisms. While the emergence of multi-drug resistance has been associated with the misuse and abuse of antimicrobials, the number of available effective drugs is decreasing and novel compounds being introduced into the market are scarce. Therefore, current available antibiotic treatments often have limited or no efficacy against healthcare-associated infections (HCAIs), and novel therapeutic strategies need to be considered. This Special Issue aims to gather papers describing novel approaches to overcome infections caused by multi-drug-resistant microorganisms and/or those producing biofilms. In this context, papers on the description of antibiotic adjuvants are particularly welcome.

Dr. Luis G. Alves
Dr. Fatima Cerqueira
Guest Editors

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Keywords

  • multidrug resistance
  • biofilm
  • drug design
  • antibiotic adjuvants
  • antimicrobial synergy

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Published Papers (4 papers)

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Research

17 pages, 2081 KiB  
Article
Identifying Potential Natural Antibiotics from Unani Formulas through Machine Learning Approaches
by Ahmad Kamal Nasution, Muhammad Alqaaf, Rumman Mahfujul Islam, Sony Hartono Wijaya, Naoaki Ono, Shigehiko Kanaya and Md. Altaf-Ul-Amin
Antibiotics 2024, 13(10), 971; https://doi.org/10.3390/antibiotics13100971 - 14 Oct 2024
Viewed by 727
Abstract
The Unani Tibb is a medical system of Greek descent that has undergone substantial dissemination since the 11th century and is currently prevalent in modern South and Central Asia, particularly in primary health care. The ingredients of Unani herbal medicines are primarily derived [...] Read more.
The Unani Tibb is a medical system of Greek descent that has undergone substantial dissemination since the 11th century and is currently prevalent in modern South and Central Asia, particularly in primary health care. The ingredients of Unani herbal medicines are primarily derived from plants. Our research aimed to address the pressing issues of antibiotic resistance, multi-drug resistance, and the emergence of superbugs by examining the molecular-level effects of Unani ingredients as potential new natural antibiotic candidates. We utilized a machine learning approach to tackle these challenges, employing decision trees, kernels, neural networks, and probability-based methods. We used 12 machine learning algorithms and several techniques for preprocessing data, such as Synthetic Minority Over-sampling Technique (SMOTE), Feature Selection, and Principal Component Analysis (PCA). To ensure that our model was optimal, we conducted grid-search tuning to tune all the hyperparameters of the machine learning models. The application of Multi-Layer Perceptron (MLP) with SMOTE pre-processing techniques resulted in an impressive accuracy precision and recall values. This analysis identified 20 important metabolites as essential components of the formula, which we predicted as natural antibiotics. In the final stage of our investigation, we verified our prediction by conducting a literature search for journal validation or by analyzing the structural similarity with known antibiotics using asymmetric similarity. Full article
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12 pages, 557 KiB  
Article
Multidrug-Resistant Escherichia coli Remains Susceptible to Metal Ions and Graphene-Based Compounds
by Nathalie Karaky, Shiying Tang, Parameshwari Ramalingam, Andrew Kirby, Andrew J. McBain, Craig E. Banks and Kathryn A. Whitehead
Antibiotics 2024, 13(5), 381; https://doi.org/10.3390/antibiotics13050381 - 24 Apr 2024
Cited by 1 | Viewed by 1564
Abstract
Escherichia coli is listed as a priority 1 pathogen on the World Health Organization (WHO) priority pathogen list. For this list of pathogens, new antibiotics are urgently needed to control the emergence and spread of multidrug-resistant strains. This study assessed eighteen metal ions, graphene, [...] Read more.
Escherichia coli is listed as a priority 1 pathogen on the World Health Organization (WHO) priority pathogen list. For this list of pathogens, new antibiotics are urgently needed to control the emergence and spread of multidrug-resistant strains. This study assessed eighteen metal ions, graphene, and graphene oxide for their antimicrobial efficacy against E. coli in both planktonic and biofilm growth states and the potential synergy between metal ions and graphene-based compounds. Molybdenum and tin ions exhibited the greatest antimicrobial activity against the planktonic states of the isolates with minimal inhibitory concentrations (MIC) ranging between 13 mg/L and 15.6 mg/L. Graphene oxide had no antimicrobial effect against any of the isolates, while graphene showed a moderate effect against E. coli (MIC, 62.5 mg/L). Combinations of metal ions and graphene-based compounds including tin–graphene, tin–graphene oxide, gold–graphene, platinum–graphene, and platinum–graphene oxide exhibited a synergistic antimicrobial effect (FIC ≤ 0.5), inhibiting the planktonic and biofilm formation of the isolates regardless of their antibiotic-resistant profiles. The bactericidal effect of the metal ions and the synergistic effects when combined with graphene/graphene oxide against medically relevant pathogens demonstrated that the antimicrobial efficacy was increased. Hence, such agents may potentially be used in the production of novel antimicrobial/antiseptic agents. Full article
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13 pages, 1986 KiB  
Article
A Cyclam Salt as an Antifungal Agent: Interference with Candida spp. and Cryptococcus neoformans Mechanisms of Virulence
by Fátima Cerqueira, Rui Medeiros, Inês Lopes, Carla Campos, Maria Pia Ferraz, Fernando Silva, Luís G. Alves and Eugénia Pinto
Antibiotics 2024, 13(3), 222; https://doi.org/10.3390/antibiotics13030222 - 28 Feb 2024
Cited by 2 | Viewed by 1755
Abstract
The importance of fungal infections, particularly those caused by yeasts, is increasing among the medical community. Candida albicans and Cryptococcus neoformans are amongst the high-priority fungal species identified by the World Health Organization (WHO) and are considered in the critical group, while Candida [...] Read more.
The importance of fungal infections, particularly those caused by yeasts, is increasing among the medical community. Candida albicans and Cryptococcus neoformans are amongst the high-priority fungal species identified by the World Health Organization (WHO) and are considered in the critical group, while Candida krusei is included in the medium-priority group. The cyclam salt H4[H2(4-CF3PhCH2)2Cyclam]Cl4 proved to be active against the growth of these three yeasts, and the aim of this work was to verify its interference with their virulence mechanisms, whether shared or unique. H4[H2(4-CF3PhCH2)2Cyclam]Cl4 significantly inhibited biofilm production and catalase activity, being able to interfere with C. albicans dimorphic transition and C. neoformans melanin production. At the minimal inhibitory concentration (MIC) values, H4[H2(4-CF3PhCH2)2Cyclam]Cl4 had no antioxidant effect, as determined by the DPPH method. When using the RAW264.7 macrophage cell line, H4[H2(4-CF3PhCH2)2Cyclam]Cl4 reduced nitric oxide (NO) detection (the Griess reaction), but this effect was associated with a significant toxic effect on the cells. Full article
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19 pages, 5562 KiB  
Article
3-Substituted Coumarins Inhibit NorA and MepA Efflux Pumps of Staphylococcus aureus
by José B. de Araújo-Neto, Cícera D. de M. Oliveira-Tintino, Gildênia A. de Araújo, Daniel S. Alves, Fernanda R. Ribeiro, Guilherme A. Brancaglion, Diogo T. Carvalho, Clara Mariana Gonçalves Lima, Hani S. H. Mohammed Ali, Irfan A. Rather, Mohmmad Y. Wani, Talha B. Emran, Henrique D. M. Coutinho, Valdir de Q. Balbino and Saulo R. Tintino
Antibiotics 2023, 12(12), 1739; https://doi.org/10.3390/antibiotics12121739 - 15 Dec 2023
Cited by 4 | Viewed by 2095
Abstract
Coumarins are compounds with scientifically proven antibacterial properties, and modifications to the chemical structure are known to improve their effects. This information is even more relevant with the unbridled advances of antibiotic resistance, where Staphylococcus aureus and its efflux pumps play a prominent [...] Read more.
Coumarins are compounds with scientifically proven antibacterial properties, and modifications to the chemical structure are known to improve their effects. This information is even more relevant with the unbridled advances of antibiotic resistance, where Staphylococcus aureus and its efflux pumps play a prominent role. The study’s objective was to evaluate the potential of synthetic coumarins with different substitutions in the C-3 position as possible inhibitors of the NorA and MepA efflux pumps of S. aureus. For this evaluation, the following steps took place: (i) the determination of the minimum inhibitory concentration (MIC); (ii) the association of coumarins with fluoroquinolones and ethidium bromide (EtBr); (iii) the assessment of the effect on EtBr fluorescence emission; (iv) molecular docking; and (v) an analysis of the effect on membrane permeability. Coumarins reduced the MICs of fluoroquinolones and EtBr between 50% and 87.5%. Coumarin C1 increased EtBr fluorescence emission between 20 and 40% by reinforcing the evidence of efflux inhibition. The molecular docking results demonstrated that coumarins have an affinity with efflux pumps and establish mainly hydrogen bonds and hydrophobic interactions. Furthermore, C1 did not change the permeability of the membrane. Therefore, we conclude that these 3-substituted coumarins act as inhibitors of the NorA and MepA efflux pumps of S. aureus. Full article
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