Alternative Approaches to Treating Antimicrobial Resistant Infections, 4th Edition

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Antibiotic Therapy in Infectious Diseases".

Deadline for manuscript submissions: 30 April 2027 | Viewed by 2225

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Guest Editor
School of Medicine and Biosciences, University of West London, Brentford TW8 9GA, UK
Interests: Targeted metabolomics; isotope labelling; microbial metabolomics; GC-MS; LC-MS; NMR
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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 The development of novel antimicrobials has slowed down in recent years, and major pharmaceutical firms have withdrawn from the field of anti-infective research due to its low profitability.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

Manuscript Submission Information

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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 (3 papers)

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Research

15 pages, 291 KB  
Article
Six Essential Oils as Potential Antibacterial Agents Against Extensively Drug-Resistant (XDR) Gram-Negative Clinical Isolates
by Bianca Bǎdescu-Chircea, Sergio Liga, Monica Licker, Dorina Dugăeşescu, Mihaela Diana Popa, Ciprian Nicolae Piluţ, Silvana Vulpie, Valentina Oana Buda and Delia Muntean
Antibiotics 2026, 15(8), 782; https://doi.org/10.3390/antibiotics15080782 - 13 Aug 2026
Viewed by 259
Abstract
Background/Objectives: Extensively drug-resistant Gram-negative pathogens severely limit antimicrobial treatment options. This study evaluated the in vitro antibacterial activity of six essential oils obtained from Romanian medicinal plants against extensively drug-resistant clinical isolates and interpreted the antibacterial findings in the context of their [...] Read more.
Background/Objectives: Extensively drug-resistant Gram-negative pathogens severely limit antimicrobial treatment options. This study evaluated the in vitro antibacterial activity of six essential oils obtained from Romanian medicinal plants against extensively drug-resistant clinical isolates and interpreted the antibacterial findings in the context of their previously reported chemical composition. Methods: Forty-one non-duplicate clinical isolates were included: (i) Acinetobacter baumannii (n = 21); (ii) Klebsiella pneumoniae (n = 14); (iii) Pseudomonas aeruginosa (n = 4); and (iv) Providencia stuartii (n = 2). The chemical composition of the six essential oils from Thymus vulgaris, Thymus pannonicus, Satureja montana, Mentha × smithiana, Mentha × piperita, and Lavandula angustifolia had been previously characterized by gas chromatography–mass spectrometry (GC-MS), and the corresponding compositional data were used in the present study. Antibacterial activity was assessed using disk-diffusion, disk-volatilization, and broth-dilution assays to determine minimum inhibitory and minimum bactericidal concentrations. Results: Satureja montana contained 60.9% carvacrol, T. vulgaris 44.6% carvacrol, and T. pannonicus 34.9% thymol. S. montana showed the strongest overall antibacterial activity, followed by T. vulgaris and T. pannonicus. A. baumannii isolates showed the greatest overall inhibitory response; S. montana produced direct-contact inhibition zones ≥ 25 mm in all 21 isolates and vapor–phase zones of 25–29 mm in 17 of 21 isolates. K. pneumoniae showed oil-dependent inhibition patterns, while the findings for the two P. stuartii isolates were interpreted descriptively because of the limited subgroup size. The four P. aeruginosa isolates showed the lowest overall inhibitory response, particularly in the vapor phase assay. MIC and MBC findings broadly supported the diffusion-based results, whereas L. angustifolia showed the weakest overall activity. Conclusions: Essential oils rich in phenolic monoterpenes, particularly those containing carvacrol or thymol, showed promising in vitro activity against extensively drug-resistant Gram-negative clinical isolates. These findings do not establish clinical efficacy and require confirmation in larger isolate collections using standardized assays, including cytotoxicity, biofilm, formulation, and synergy studies. Full article
30 pages, 6241 KB  
Article
A Trehalose-Based Phenotypic Screen Identifies Candidate Inhibitors of Mycobacterium tuberculosis Recycling Pathway
by Rebecca Vande Voorde, Aaron M. Maves, Dylan Nelson and Lia Danelishvili
Antibiotics 2026, 15(8), 743; https://doi.org/10.3390/antibiotics15080743 - 31 Jul 2026
Viewed by 347
Abstract
Background/Objectives: Phenotypic drug tolerance, distinct from genetic resistance, allows Mycobacterium tuberculosis (Mtb) to survive prolonged antibiotic exposure and contributes to treatment failure and relapse. The trehalose recycling pathway, mediated by the LpqY-SugABC transporter, has been implicated as a metabolic “escape” mechanism that [...] Read more.
Background/Objectives: Phenotypic drug tolerance, distinct from genetic resistance, allows Mycobacterium tuberculosis (Mtb) to survive prolonged antibiotic exposure and contributes to treatment failure and relapse. The trehalose recycling pathway, mediated by the LpqY-SugABC transporter, has been implicated as a metabolic “escape” mechanism that sustains Mtb viability under antibiotic and nutrient-limiting stress, making it an attractive target for adjunctive, tolerance-breaking therapeutics. Methods and Results: Here, we conducted a high-throughput phenotypic screen of 50,000 compounds from chemically diverse libraries, using a carbon source-restricted assay that forces Mtb to rely on trehalose uptake for growth, to identify small-molecule inhibitors of this pathway. This approach yielded 23 confirmed hits in Mtb, spanning several chemical scaffolds, including thioureas, propanamides, benzamides, and carboxamides. Using an isogenic set of Mtb wild-type, LpqY-SugABC transposon knockout, and complemented strains, we confirmed that the genetic loss of transporter loss reproduces accelerated killing by isoniazid, rifampicin, and bedaquiline, but not moxifloxacin, and that loss of trehalose recycling sensitizes mycobacteria to oxidative stress. Using orthogonal functional assays, fluorescent trehalose probe (FITC-tre) uptake inhibition and H2O2 hypersensitization, thiourea-containing compounds emerged as the candidates most consistent with transporter-specific activity, phenocopying the effects of genetic LpqY-SugABC loss, while biochemical assays against recombinant trehalase (Rv2402) excluded downstream enzymatic inhibition as their mechanism of action. In addition, several hits potentiated rifampicin-mediated killing of intracellular Mtb in THP-1 macrophages, in some cases reducing bacterial burden below levels achieved by monotherapy. Conclusions: These findings indicate that the trehalose recycling pathway is functionally druggable by small molecules identified through unbiased phenotypic screening and nominate thiourea- and propanamide-based scaffolds as priority candidates for further mechanistic characterization, including direct target-engagement studies, and optimization as adjunctive anti-tuberculosis agents targeting drug-tolerant Mtb populations. Full article
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15 pages, 530 KB  
Article
Antibiotic Adjuvant Potential of Selected Essential Oil Components Against Respiratory Pathogens: From Planktonic Synergy to Early-Stage Biofilm Inhibition
by Viktória Lilla Balázs, Rita Filep, Edit Ormai, Lilla Radványi, Béla Kocsis, Erika Kerekes and Marianna Kocsis
Antibiotics 2026, 15(4), 403; https://doi.org/10.3390/antibiotics15040403 - 16 Apr 2026
Viewed by 1184
Abstract
Background: Respiratory tract infections remain among the most common indications for antibiotic therapy and represent a major driver of antimicrobial resistance. The ability of respiratory pathogens to form biofilms further contributes to treatment failure and recurrence. This study aimed to evaluate the antibiotic [...] Read more.
Background: Respiratory tract infections remain among the most common indications for antibiotic therapy and represent a major driver of antimicrobial resistance. The ability of respiratory pathogens to form biofilms further contributes to treatment failure and recurrence. This study aimed to evaluate the antibiotic adjuvant potential of selected essential oil components against clinically relevant respiratory bacteria and to determine whether planktonic synergistic interactions translate into early-stage antibiofilm efficacy. Thymol, eugenol, trans-cinnamaldehyde, and terpinen-4-ol were tested against Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, methicillin-resistant Staphylococcus aureus (MRSA), and Pseudomonas aeruginosa. Methods: Minimum inhibitory concentrations were determined by broth microdilution. Synergistic interactions with clinically relevant antibiotics were assessed using the checkerboard method and fractional inhibitory concentration index (FICI) analysis. Selected combinations were further evaluated in a 6 h crystal violet-based early-stage biofilm model. Gram-positive strains generally exhibited higher susceptibility to the tested components than Gram-negative bacteria. Results: Synergistic interactions (FICI ≤ 0.5) were most frequently observed between β-lactam antibiotics and phenolic components, particularly thymol and trans-cinnamaldehyde. Strong synergy was detected for vancomycin-eugenol against MRSA and for amoxicillin/clavulanic acid–cinnamaldehyde against M. catarrhalis. Importantly, synergistic combinations translated into significantly enhanced inhibition of early biofilm formation, increasing inhibition rates by 15–40% compared to antibiotic monotherapy (p < 0.05). Selected essential oil components enhanced the antibacterial activity of clinically relevant antibiotics and effectively potentiated early-stage biofilm inhibition. Conclusions: These findings support further investigation of phytochemical-antibiotic combinations as potential adjunct strategies in respiratory infection management. Full article
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