Alternative Approaches to Treating Antimicrobial Resistant Infections, 3rd Edition

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Department of Life Sciences, University of Roehampton, London, UK
Interests: metabolic evolution; opportunistic pathogens; cystic fibrosis; Pseudomonas aeruginosa; Staphylococcus aureus
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Special Issue Information

Dear Colleagues,

This Special Issue will focus on alternative approaches to treating antimicrobial-resistant infections. The discovery of antibiotics revolutionized the clinical treatment of bacterial infections; however, this fundamental pillar of modern medicine is now crumbling. The development of novel antimicrobials has slowed down in recent years and major pharmaceutical firms have withdrawn from the field of anti-infective research due to its low profitability.

As a consequence, many infections are now difficult to treat, which is raising mortality and healthcare-associated costs due to difficulties in accomplishing total remission. Antimicrobial resistance is now considered to be one of the greatest risks to humanity. Common surgical procedures and treatments that could lead to immunosuppression may soon be considered high-risk due to the antibiotic crisis (e.g., cancer chemotherapy or organ transplants).

We are therefore inviting both reviews and original articles on the latest developments in novel antibacterial strategies with which to treat infections caused by antimicrobial-resistant pathogens. Topics include the development of novel combinatorial therapies based on the repurposing of anti-infectives, host-targeted therapies, bacteriophages, the use of predatory bacteria, bacteriocins, antimicrobial peptides, nanoparticles, natural compounds, immunotherapeutics, probiotics used for the competitive exclusion of pathogens, and the development of novel antibacterial compounds.

Dr. Michal Letek
Dr. Volker Behrends
Guest Editors

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Keywords

  • repurposing
  • anti-infectives
  • host-targeted therapies
  • bacteriophages
  • predatory bacteria
  • bacteriocins
  • antimicrobial peptides
  • nanoparticles
  • natural compounds
  • immunotherapy
  • probiotics
  • antibiotics

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Related Special Issue

Published Papers (4 papers)

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Research

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11 pages, 5688 KiB  
Article
Probiotic-Loaded Bacterial Cellulose as an Alternative to Combat Carbapenem-Resistant Bacterial Infections
by José Gutiérrez-Fernández, Laura Cerezo-Collado, Víctor Garcés, Pablo Alarcón-Guijo, José M. Delgado-López and Jose M. Dominguez-Vera
Antibiotics 2024, 13(11), 1003; https://doi.org/10.3390/antibiotics13111003 - 25 Oct 2024
Viewed by 915
Abstract
Background: Carbapenems are one of the mainstays of treatment for antibiotic-resistant bacteria (ARB). This has made the rise of carbapenem-resistant bacteria a threat to global health. In fact, the World Health Organization (WHO) has identified carbapenem-resistant bacteria as critical pathogens, and the development [...] Read more.
Background: Carbapenems are one of the mainstays of treatment for antibiotic-resistant bacteria (ARB). This has made the rise of carbapenem-resistant bacteria a threat to global health. In fact, the World Health Organization (WHO) has identified carbapenem-resistant bacteria as critical pathogens, and the development of novel antibacterials capable of combating infections caused by these bacteria is a priority. Objective: With the aim of finding new alternatives to fight against ARB and especially against carbapenem-resistant bacteria, we have developed a series of living materials formed by incorporating the probiotics Lactobacillus plantarum (Lp), Lactobacillus fermentum (Lf), and a mixture of both (L. plantarum+L. fermentum) into bacterial cellulose (BC). Results: These probiotic-loaded bacterial celluloses inhibited the proliferation of three ARB, including two carbapenem-resistant enterobacteria (CRE), identified as Klebsiella pneumoniae and Enterobacter cloacae, and a carbapenem-resistant Pseudomonas aeruginosa. Interestingly, while the probiotics L. plantarum, L. fermentum, and the mixture of both were found to be inactive against these ARB, they became active once incorporated into BC. Conclusions: The increase in activity is due to the known effect that cells increase their activity once incorporated into a suitable matrix, forming a living material. For the same reasons, the probiotics in the living materials BC–L. plantarum, BC–L. fermentum, and BC–L. plantarum+L. fermentum showed increased stability, allowing them to be stored with bacterial activity for long periods of time (two months). Full article
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20 pages, 12440 KiB  
Article
Synergistic Activity of Ingulados Bacteria with Antibiotics against Multidrug-Resistant Pathogens
by Javier Blanco-Blanco, María Bravo, Irene Simón, Pedro Fernández-Llario, Miguel Fajardo-Olivares, María Coronada Fernández-Calderón and Rosario Cerrato
Antibiotics 2024, 13(3), 200; https://doi.org/10.3390/antibiotics13030200 - 20 Feb 2024
Cited by 1 | Viewed by 2448
Abstract
Antimicrobial resistance is a critical challenge due to the overuse of conventional antimicrobials, and alternative solutions are urgently needed. This study investigates the efficacy of compounds derived from lactic acid bacteria (LAB) fermentation combined with antibiotics against multidrug-resistant pathogens isolated from clinical cases [...] Read more.
Antimicrobial resistance is a critical challenge due to the overuse of conventional antimicrobials, and alternative solutions are urgently needed. This study investigates the efficacy of compounds derived from lactic acid bacteria (LAB) fermentation combined with antibiotics against multidrug-resistant pathogens isolated from clinical cases in a hospital setting. Strains of Escherichia coli, Klebsiella pneumoniae, and Enterococcus faecium and faecalis were isolated and selected from blood, respiratory, and urine samples. They were tested against the fermentation products from the Ingulados LAB collection (BAL5, BAL6, BAL8, BAL13, and BAL16), recognized for their antimicrobial efficacy against veterinary pathogens. The activity against multidrug-resistant (MDR) pathogens was evaluated initially, followed by synergy tests using checkerboard assays and subsequent analysis. Bioinformatic assessments and supernatant treatments were performed to characterize the nature of the compounds responsible for the antimicrobial activity. Notably, BAL16 exhibited significant growth inhibition against multidrug-resistant E. faecium. Synergy tests highlighted its combined activity with tetracycline through FICI and surface analysis and bioinformatic analysis unveiled the protein fraction containing bacteriocins as the underlying mechanism. This study highlights BAL16 fermentation products potential as valuable antimicrobial agents against MDR E. faecium infections, attributed to bacteriocins. Further in-depth studies are necessary for complete bacteriocin characterization. Full article
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Review

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16 pages, 1531 KiB  
Review
Innovative Strategies in Drug Repurposing to Tackle Intracellular Bacterial Pathogens
by Blanca Lorente-Torres, Jesús Llano-Verdeja, Pablo Castañera, Helena Á. Ferrero, Sergio Fernández-Martínez, Farzaneh Javadimarand, Luis M. Mateos, Michal Letek and Álvaro Mourenza
Antibiotics 2024, 13(9), 834; https://doi.org/10.3390/antibiotics13090834 - 2 Sep 2024
Viewed by 1252
Abstract
Intracellular bacterial pathogens pose significant public health challenges due to their ability to evade immune defenses and conventional antibiotics. Drug repurposing has recently been explored as a strategy to discover new therapeutic uses for established drugs to combat these infections. Utilizing high-throughput screening, [...] Read more.
Intracellular bacterial pathogens pose significant public health challenges due to their ability to evade immune defenses and conventional antibiotics. Drug repurposing has recently been explored as a strategy to discover new therapeutic uses for established drugs to combat these infections. Utilizing high-throughput screening, bioinformatics, and systems biology, several existing drugs have been identified with potential efficacy against intracellular bacteria. For instance, neuroleptic agents like thioridazine and antipsychotic drugs such as chlorpromazine have shown effectiveness against Staphylococcus aureus and Listeria monocytogenes. Furthermore, anticancer drugs including tamoxifen and imatinib have been repurposed to induce autophagy and inhibit bacterial growth within host cells. Statins and anti-inflammatory drugs have also demonstrated the ability to enhance host immune responses against Mycobacterium tuberculosis. The review highlights the complex mechanisms these pathogens use to resist conventional treatments, showcases successful examples of drug repurposing, and discusses the methodologies used to identify and validate these drugs. Overall, drug repurposing offers a promising approach for developing new treatments for bacterial infections, addressing the urgent need for effective antimicrobial therapies. Full article
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22 pages, 1296 KiB  
Review
Bacteriophage Therapy in Companion and Farm Animals
by Laura Bianchessi, Giulia De Bernardi, Martina Vigorelli, Paola Dall’Ara and Lauretta Turin
Antibiotics 2024, 13(4), 294; https://doi.org/10.3390/antibiotics13040294 - 23 Mar 2024
Cited by 2 | Viewed by 3113
Abstract
Bacteriophages, which are viruses with restricted tropism for bacteria, have been employed for over a century as antimicrobial agents; they have been largely abandoned in Western countries but are constantly used in Eastern European countries with the advent of antibiotics. In recent decades, [...] Read more.
Bacteriophages, which are viruses with restricted tropism for bacteria, have been employed for over a century as antimicrobial agents; they have been largely abandoned in Western countries but are constantly used in Eastern European countries with the advent of antibiotics. In recent decades, the growing spread of multidrug-resistant bacteria, which pose a serious threat to worldwide public health, imposed an urgent demand for alternative therapeutic approaches to antibiotics in animal and human fields. Based on this requirement, numerous studies have been published on developing and testing bacteriophage-based therapy. Overall, the literature largely supports the potential of this perspective but also highlights the need for additional research as the current standards are inadequate to receive approval from regulatory authorities. This review aims to update and critically revise the current knowledge on the application of bacteriophages to treat bacterial-derived infectious diseases in animals in order to provide topical perspectives and innovative advances. Full article
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