New Strategies for Antimicrobial Treatment

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Antimicrobial Agents and Resistance".

Deadline for manuscript submissions: closed (31 March 2026) | Viewed by 4614

Special Issue Editor


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Guest Editor
College of Pharmaceutical Sciences, Southwest University, Chongqing, China
Interests: metal-based novel antimicrobial agents and their targeted therapy

Special Issue Information

Dear Colleagues,

This Special Issue is dedicated to advancing the field of antimicrobial treatments by highlighting innovative strategies to counteract antimicrobial resistance. It aims to consolidate groundbreaking research on new antimicrobial agents, their unique mechanisms, and environmental implications. The Issue actively promotes interdisciplinary collaboration among microbiologists, pharmacologists, molecular biologists, and clinicians to hasten the transition of research findings into clinical applications. It seeks to widely disseminate cutting-edge findings to refine existing treatments and inspire the creation of novel therapeutic options. Contributions are invited on alternative therapies, resistance mechanisms, and combination therapies that enhance efficacy and minimize resistance development. The inclusion of diverse clinical trials and case studies will offer valuable insights into treatment effectiveness. Additionally, the Issue will emphasize the importance of pharmacokinetic and pharmacodynamic studies for personalized medicine and robust preclinical research to support clinical trials.

Dr. Chen Fu
Guest Editor

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Keywords

  • antimicrobial treatments
  • antimicrobial resistance
  • innovative strategies
  • new antimicrobial agents
  • clinical applications
  • alternative therapies
  • resistance mechanisms
  • combination therapies

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Published Papers (3 papers)

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Research

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15 pages, 1450 KB  
Article
A New Endolysin Lys59: A Broad-Spectrum Phage Endolysin Targeting Both Gram-Negative and Gram-Positive Bacteria
by Yunhan Zhang, Chenwei Deng, Yanni Liu, Weiqing Lan, Yong Zhao and Xiaohong Sun
Microorganisms 2026, 14(5), 1027; https://doi.org/10.3390/microorganisms14051027 - 30 Apr 2026
Viewed by 2
Abstract
To address the emerging multidrug-resistance crisis caused by Klebsiella pneumoniae, we expressed the endolysin Lys59 derived from phage VB_KpP_HS106 and performed a comprehensive analysis of its antibacterial activity and structural features. Molecular modeling revealed that Lys59 carries a highly positively charged N-terminus [...] Read more.
To address the emerging multidrug-resistance crisis caused by Klebsiella pneumoniae, we expressed the endolysin Lys59 derived from phage VB_KpP_HS106 and performed a comprehensive analysis of its antibacterial activity and structural features. Molecular modeling revealed that Lys59 carries a highly positively charged N-terminus and an amphipathic helix at the C-terminus. In vitro antibacterial assays showed that Lys59 exhibited significant bactericidal activity against K. pneumoniae with an approximately 4 log reduction at 50 µg/mL in 2 h. Meanwhile, Lys59 exhibited potent, broad-spectrum activity against both Gram-negative and Gram-positive bacteria. Stability analysis indicated that Lys59 retained high activity over a pH range of 3–9 and a temperature range of 4–55 °C. Notably, the antibacterial activity of Lys59 was found to be regulated by metal ions. Molecular docking indicated that K+ can enhance binding stability by interacting with ASN35 and VAL57. In contrast, Mg2+ and Ca2+ suppressed catalytic function by binding to the essential GLU17 residue. Furthermore, treatment with 200 µg/mL of Lys59 resulted in a 44.6% reduction in K. pneumoniae biofilm biomass. Overall, this study identified a phage-derived endolysin with broad-spectrum antimicrobial activity and demonstrated its potential as an antibacterial agent against multidrug-resistant K. pneumoniae. Full article
(This article belongs to the Special Issue New Strategies for Antimicrobial Treatment)
20 pages, 3143 KB  
Article
Fisetin as an Antiviral Agent Targeting the RNA-Dependent RNA Polymerase of SARS-CoV-2: Computational Prediction and In Vitro Experimental Validation
by Ximena Hernández-Rodríguez, Flor Itzel Lira-Hernández, José Manuel Reyes-Ruíz, Juan Fidel Osuna-Ramos, Carlos Noe Farfán-Morales, Daniela Nahomi Calderón-Sandate, Julio Enrique Castañeda-Delgado, Moisés León-Juárez, Rosa María del Ángel, Bruno Rivas-Santiago, Saúl Noriega, David Mauricio Cañedo-Figueroa, Sarita Montaño, Alan Orlando Santos-Mena, Ana Cristina García-Herrera and Luis Adrián De Jesús-González
Microorganisms 2025, 13(12), 2809; https://doi.org/10.3390/microorganisms13122809 - 10 Dec 2025
Cited by 1 | Viewed by 934
Abstract
SARS-CoV-2 continues to evolve into immune-evasive variants, and although vaccination remains the cornerstone of prevention, the search for antiviral molecules targeting conserved viral enzymes remains essential. The RNA-dependent RNA polymerase (NSP12) is a central component of coronavirus replication, and natural polyphenols have been [...] Read more.
SARS-CoV-2 continues to evolve into immune-evasive variants, and although vaccination remains the cornerstone of prevention, the search for antiviral molecules targeting conserved viral enzymes remains essential. The RNA-dependent RNA polymerase (NSP12) is a central component of coronavirus replication, and natural polyphenols have been recurrently proposed as modulators of viral polymerases. Among these compounds, Fisetin has been reported to interact with multiple viral and cellular pathways, yet its direct antiviral activity against SARS-CoV-2 remained largely unexplored. Here, we first analyzed the interaction of Fisetin with the catalytic and NiRAN domains of NSP12 using molecular docking and molecular dynamics simulations, revealing stable and energetically favorable binding throughout a 100 ns simulation. Previous biochemical reports have shown that Fisetin inhibits the recombinant SARS-CoV-2 RdRp, supporting its potential to engage the polymerase. We then evaluated its antiviral activity in human A549 lung epithelial cells infected with the Omicron JN.1 variant. We observed a clear dose-dependent reduction in viral infection, achieving up to 91.9% inhibition at 3 μM while maintaining acceptable cell viability. In addition, Fisetin displayed a selectivity index superior to that of Lopinavir, the positive antiviral control used in this study. Altogether, our findings demonstrate that Fisetin possesses reproducible antiviral activity in a physiologically relevant human lung model and support its role as a natural scaffold for the rational development of polymerase-targeting antivirals against emerging SARS-CoV-2 variants. Full article
(This article belongs to the Special Issue New Strategies for Antimicrobial Treatment)
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Review

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18 pages, 1602 KB  
Review
Mechanisms Operating in the Use of Transition Metal Complexes to Combat Antimicrobial Resistance
by Shiming Wu, Meishu Wang, Ziyi Liu and Chen Fu
Microorganisms 2025, 13(7), 1570; https://doi.org/10.3390/microorganisms13071570 - 3 Jul 2025
Cited by 16 | Viewed by 3070
Abstract
The increasing diversity and escalating drug resistance of bacterial pathogens have significantly compromised the efficacy of conventional antimicrobial agents, creating formidable challenges in modern infection control. These developments underscore the critical need for innovative therapeutic strategies to address the persistent global health burden [...] Read more.
The increasing diversity and escalating drug resistance of bacterial pathogens have significantly compromised the efficacy of conventional antimicrobial agents, creating formidable challenges in modern infection control. These developments underscore the critical need for innovative therapeutic strategies to address the persistent global health burden posed by microbial resistance. While metal-based compounds have been extensively studied for their anticancer properties in clinical applications, their potential in antimicrobial contexts remains relatively underexplored. This review systematically elaborates on the structure-activity relationship of metal complexes, with a focus on the unique characteristics of metal drugs that differ from organic small molecules. These drugs can overcome drug resistance through various mechanisms (such as generation of reactive oxygen species and penetration of biological membranes). Understanding these mechanisms provides a crucial basis for guiding ligand design and the development of delivery systems. Full article
(This article belongs to the Special Issue New Strategies for Antimicrobial Treatment)
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