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Antibiotics
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Recent Advances in Antimicrobial Drug Discovery, 2nd Volume
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Recent Advances in Antimicrobial Drug Discovery, 2nd Volume

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Novel Antimicrobial Agents".

Deadline for manuscript submissions: 31 August 2024 | Viewed by 5430

Special Issue Editors

Dr. Melissa M. Cadelis

E-Mail Website
Guest Editor
School of Medical Sciences, University of Auckland, Auckland 1142, New Zealand
Interests: natural product; medicinal chemistry; organic chemistry
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Anna Zanfardino

E-Mail Website
Guest Editor
Department of Biology, University of Naples Federico II, Via Cintia, 80126 Naples, Italy
Interests: antimicrobials; antibiofilm compounds; antioxidants; anti-inflammatory molecules

Special Issue Information

Dear Colleagues,

The rise of multi-drug resistant (MDR) bacteria has evolved into a grave worldwide concern, leading to higher rates of illness and death among those affected. This has had detrimental effects on public health and the economy. The diminishing availability of effective drugs to combat these infections has severely limited treatment options, emphasizing the immediate requirement for innovative strategies with novel mechanisms of action. Such approaches are essential to address the wide array of antimicrobial resistance mechanisms displayed by these MDR pathogens. The key to managing this crisis is the discovery of new antibiotics.

It is widely accepted that around half of all prescribed medications come from natural sources such as plants, marine life, and microorganisms. Natural products have been instrumental in delivering significant medical advancements in recent years. Considering the success of the previous volume, we now invite the submission of research and review articles focused on the exploration of natural products or synthetic derivatives that exhibit antibacterial activities. We also encourage studies that elucidate the mechanisms and modes of action behind their antibacterial properties.

Dr. Melissa M. Cadelis
Prof. Dr. Anna Zanfardino
Guest Editors

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.

Related Special Issue

Published Papers (4 papers)

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Research

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16 pages, 4461 KiB  
Article
Natural Products Biosynthesis by Streptomyces netropsis IMV Ac-5025 under Exogenous Sterol Action
by Mariia Loboda, Liudmyla Biliavska, Galyna Iutynska, Jake Newitt and Ruslan Mariychuk
Antibiotics 2024, 13(2), 146; https://doi.org/10.3390/antibiotics13020146 - 01 Feb 2024
Viewed by 943
Abstract
Streptomycetes are known as producers of bioactive substances, particularly antibiotics. Streptomyces netropsis IMV Ac-5025 simultaneously produces different classes of antibiotics, including polyene compounds, phytohormones, and sterols, but the metabolic pathways involved in their biosynthesis are largely understudied. The aim of this work was [...] Read more.
Streptomycetes are known as producers of bioactive substances, particularly antibiotics. Streptomyces netropsis IMV Ac-5025 simultaneously produces different classes of antibiotics, including polyene compounds, phytohormones, and sterols, but the metabolic pathways involved in their biosynthesis are largely understudied. The aim of this work was to explore the biosynthesis of polyene antibiotics, sterols, and phytohormones when the producer is cultivated in a nutrient medium supplemented with exogenous β-sitosterol. Gas chromatography and high-performance liquid chromatography were applied to analyze the spectrum of bioactive compounds. The obtained results demonstrated not only an increase in the accumulation of biomass but also polyene antibiotics, intracellular sterols, auxins, and cytokinins, when cultivating S. netropsis IMV Ac-5025 in a liquid medium with the addition of β-sitosterol. The amount of biomass raised 1.5–2-fold, whilst the sum of polyene antibiotics increased 4.5-fold, sterols’ sum (ergosterol, cholesterol, stigmasterol, β-sitosterol, and 24-epibrassinolide) by 2.9-fold, auxins’ sum (indole-3-acetic acid, indole-3-acetic acid hydrazide, indole-3-carbinol, indole-3-butyric acid, indole-3-carboxaldehyde, and indole-3-carboxylic acid) by 6-fold, and cytokinins’ sum (zeatin, isopentyladenine, zeatin riboside, and isopentenyladenosine) by 11-fold. Thus, we put forward the hypothesis that β-sitosterol plays a regulatory role in the network of biosynthetic reactions of S. netropsis IMV Ac-5025. Full article
(This article belongs to the Special Issue Recent Advances in Antimicrobial Drug Discovery, 2nd Volume)
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22 pages, 1837 KiB  
Article
GATR-3, a Peptide That Eradicates Preformed Biofilms of Multidrug-Resistant Acinetobacter baumannii
by Monique L. van Hoek, Fahad M. Alsaab and Ashley M. Carpenter
Antibiotics 2024, 13(1), 39; https://doi.org/10.3390/antibiotics13010039 - 31 Dec 2023
Viewed by 1608
Abstract
Acinetobacter baumannii is a gram-negative bacterium that causes hospital-acquired and opportunistic infections, resulting in pneumonia, sepsis, and severe wound infections that can be difficult to treat due to antimicrobial resistance and the formation of biofilms. There is an urgent need to develop novel [...] Read more.
Acinetobacter baumannii is a gram-negative bacterium that causes hospital-acquired and opportunistic infections, resulting in pneumonia, sepsis, and severe wound infections that can be difficult to treat due to antimicrobial resistance and the formation of biofilms. There is an urgent need to develop novel antimicrobials to tackle the rapid increase in antimicrobial resistance, and antimicrobial peptides (AMPs) represent an additional class of potential agents with direct antimicrobial and/or host-defense activating activities. In this study, we present GATR-3, a synthetic, designed AMP that was modified from a cryptic peptide discovered in American alligator, as our lead peptide to target multidrug-resistant (MDR) A. baumannii. Antimicrobial susceptibility testing and antibiofilm assays were performed to assess GATR-3 against a panel of 8 MDR A. baumannii strains, including AB5075 and some clinical strains. The GATR-3 mechanism of action was determined to be via loss of membrane integrity as measured by DiSC3(5) and ethidium bromide assays. GATR-3 exhibited potent antimicrobial activity against all tested multidrug-resistant A. baumannii strains with rapid killing. Biofilms are difficult to treat and eradicate. Excitingly, GATR-3 inhibited biofilm formation and, more importantly, eradicated preformed biofilms of MDR A. baumannii AB5075, as evidenced by MBEC assays and scanning electron micrographs. GATR3 did not induce resistance in MDR A. baumannii, unlike colistin. Additionally, the toxicity of GATR-3 was evaluated using human red blood cells, HepG2 cells, and waxworms using hemolysis and MTT assays. GATR-3 demonstrated little to no cytotoxicity against HepG2 and red blood cells, even at 100 μg/mL. GATR-3 injection showed little toxicity in the waxworm model, resulting in a 90% survival rate. The therapeutic index of GATR-3 was estimated (based on the HC50/MIC against human RBCs) to be 1250. Overall, GATR-3 is a promising candidate to advance to preclinical testing to potentially treat MDR A. baumannii infections. Full article
(This article belongs to the Special Issue Recent Advances in Antimicrobial Drug Discovery, 2nd Volume)
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15 pages, 2157 KiB  
Article
Preclinical Evaluation of Nitroxide-Functionalised Ciprofloxacin as a Novel Antibiofilm Drug Hybrid for Urinary Tract Infections
by Sophia Hawas, Jilong Qin, Sandra Wiedbrauk, Kathryn Fairfull-Smith and Makrina Totsika
Antibiotics 2023, 12(10), 1479; https://doi.org/10.3390/antibiotics12101479 - 22 Sep 2023
Viewed by 1011
Abstract
Urinary tract infections (UTIs) are the second most common bacterial infection with high recurrence rates and can involve biofilm formation on patient catheters. Biofilms are inherently tolerant to antimicrobials, making them difficult to eradicate. Many antibiofilm agents alone do not have bactericidal activity; [...] Read more.
Urinary tract infections (UTIs) are the second most common bacterial infection with high recurrence rates and can involve biofilm formation on patient catheters. Biofilms are inherently tolerant to antimicrobials, making them difficult to eradicate. Many antibiofilm agents alone do not have bactericidal activity; therefore, linking them to antibiotics is a promising antibiofilm strategy. However, many of these hybrid agents have not been tested in relevant preclinical settings, limiting their potential for clinical translation. Here, we evaluate a ciprofloxacin di-nitroxide hybrid (CDN11), previously reported to have antibiofilm activity against uropathogenic Escherichia coli (UPEC) strain UTI89 in vitro, as a potential UTI therapeutic using multiple preclinical models that reflect various aspects of UTI pathogenesis. We report improved in vitro activity over the parent drug ciprofloxacin against mature UTI89 biofilms formed inside polyethylene catheters. In bladder cell monolayers infected with UTI89, treatment with CDN11 afforded significant reduction in bacterial titers, including intracellular UPEC. Infected mouse bladders containing biofilm-like intracellular reservoirs of UPEC UTI89 showed decreased bacterial loads after ex vivo bladder treatment with CDN11. Activity for CDN11 was reported across different models of UTI, showcasing nitroxide–antibiotic hybridization as a promising antibiofilm approach. The pipeline we described here could be readily used in testing other new therapeutic compounds, fast-tracking the development of novel antibiofilm therapeutics. Full article
(This article belongs to the Special Issue Recent Advances in Antimicrobial Drug Discovery, 2nd Volume)
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Review

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28 pages, 1373 KiB  
Review
Antimicrobial Properties of Colostrum and Milk
by Furkan Eker, Emir Akdaşçi, Hatice Duman, Yalçın Mert Yalçıntaş, Ahmet Alperen Canbolat, Arda Erkan Kalkan, Sercan Karav and Dunja Šamec
Antibiotics 2024, 13(3), 251; https://doi.org/10.3390/antibiotics13030251 - 11 Mar 2024
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Abstract
The growing number of antibiotic resistance genes is putting a strain on the ecosystem and harming human health. In addition, consumers have developed a cautious attitude towards chemical preservatives. Colostrum and milk are excellent sources of antibacterial components that help to strengthen the [...] Read more.
The growing number of antibiotic resistance genes is putting a strain on the ecosystem and harming human health. In addition, consumers have developed a cautious attitude towards chemical preservatives. Colostrum and milk are excellent sources of antibacterial components that help to strengthen the immunity of the offspring and accelerate the maturation of the immune system. It is possible to study these important defenses of milk and colostrum, such as lactoferrin, lysozyme, immunoglobulins, oligosaccharides, etc., as biotherapeutic agents for the prevention and treatment of numerous infections caused by microbes. Each of these components has different mechanisms and interactions in various places. The compound’s mechanisms of action determine where the antibacterial activity appears. The activation of the antibacterial activity of milk and colostrum compounds can start in the infant’s mouth during lactation and continue in the gastrointestinal regions. These antibacterial properties possess potential for therapeutic uses. In order to discover new perspectives and methods for the treatment of bacterial infections, additional investigations of the mechanisms of action and potential complexes are required. Full article
(This article belongs to the Special Issue Recent Advances in Antimicrobial Drug Discovery, 2nd Volume)
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