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Chemical Biology of Antimicrobial Resistance, 2nd Edition

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Cross-Field Chemistry".

Deadline for manuscript submissions: 30 April 2025 | Viewed by 999

Special Issue Editor


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Guest Editor
National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, College of Life Sciences, Nankai University, Tianjin 300071, China
Interests: novel pathogen; magnetic assembly; magnetic separation; synthetic microbe; rhizosphere microbiome; antimicrobial therapy
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Special Issue Information

Dear Colleagues,

The O’Neill report on antimicrobial resistance (AMR) projects that by 2050, AMR could be responsible for up to 10 million deaths annually. ESKAPE pathogens—Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species—have already led to hundreds of fatalities. These pathogens have further evolved into multidrug-resistant strains, including Klebsiella pneumoniae carbapenemase (KPC)-producing bacteria, Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant Enterococci (VRE), for which no effective treatments currently exist. Concurrently, drug-resistant pathogenic fungi such as Candida albicans, Candida auris, and Aspergillus fumigatus are emerging as significant threats to clinical patients.

Given the urgency of this situation, there is a critical need to develop new therapeutics targeting these deadly multidrug-resistant pathogens through novel mechanisms of action. This Special Issue seeks to gather research in chemical biology aimed at addressing this global crisis, which could lead to unprecedented consequences. The scope includes the discovery of new drug-resistant genes and their underlying mechanisms, the environmental distribution and transmission of MDR genes, strategies to control the environmental spread of MDR genes and pathogens, molecular probes for studying antimicrobial resistance and antibiotic mechanisms, novel diagnostic methods, antibiotic molecules with innovative modes of action, and new antibiotic strategies and targets.

Submissions of manuscripts presenting original research in the expansive field of chemical biology are welcome. I anticipate that this Special Issue will offer valuable and distinctive insights into the pressing challenge of antimicrobial resistance.

Prof. Dr. Qilin Yu
Guest Editor

Manuscript Submission Information

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Keywords

  • antimicrobial resistance
  • resistance mechanism
  • antibiotics
  • diagnostics
  • new mode of action
  • antibiotic target
  • structure–activity relationship
  • molecular probe

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Related Special Issue

Published Papers (2 papers)

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Research

19 pages, 1632 KiB  
Article
New Conjugates of Vancomycin with Cell-Penetrating Peptides—Synthesis, Antimicrobial Activity, Cytotoxicity, and BBB Permeability Studies
by Jarosław Ruczyński, Katarzyna Prochera, Natalia Kaźmierczak, Katarzyna Kosznik-Kwaśnicka, Lidia Piechowicz, Piotr Mucha and Piotr Rekowski
Molecules 2024, 29(23), 5519; https://doi.org/10.3390/molecules29235519 - 22 Nov 2024
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Abstract
Vancomycin (Van) is a glycopeptide antibiotic commonly used as a last resort for treating life-threatening infections caused by multidrug-resistant bacterial strains, such as Staphylococcus aureus and Enterococcus spp. However, its effectiveness is currently limited due to the rapidly increasing number of drug-resistant clinical [...] Read more.
Vancomycin (Van) is a glycopeptide antibiotic commonly used as a last resort for treating life-threatening infections caused by multidrug-resistant bacterial strains, such as Staphylococcus aureus and Enterococcus spp. However, its effectiveness is currently limited due to the rapidly increasing number of drug-resistant clinical strains and its inherent cytotoxicity and poor penetration into cells and specific regions of the body, such as the brain. One of the most promising strategies to enhance its efficacy appears to be the covalent attachment of cell-penetrating peptides (CPPs) to the Van structure. In this study, a series of vancomycin conjugates with CPPs—such as TP10, Tat (47–57), PTD4, and Arg9—were designed and synthesized. These conjugates were tested for antimicrobial activity against four reference strains (Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, and Pseudomonas aeruginosa) and two clinical drug-resistant strains: methicillin-resistant S. aureus and vancomycin-resistant E. faecium. In addition, cytotoxicity tests (using a human fibroblast cell line) and blood–brain barrier (BBB) permeability tests (using a parallel artificial membrane permeability assay—PAMPA-BBB assay) were conducted for selected compounds. Our research demonstrated that conjugation of Van with CPPs, particularly with Tat (47–57), Arg9, or TP10, significantly enhances its antimicrobial activity against Gram-positive bacteria such as S. aureus and Enterococcus spp., reduces its cytotoxicity, and improves its access to brain tissues. We conclude that these findings provide a strong foundation for the design of novel antimicrobial agents effective in treating infections caused by drug-resistant staphylococcal and enterococcal strains, while also being capable of crossing the BBB. Full article
(This article belongs to the Special Issue Chemical Biology of Antimicrobial Resistance, 2nd Edition)
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12 pages, 3447 KiB  
Article
Adhesin Antibody-Grafted Mesoporous Silica Nanoparticles Suppress Immune Escape for Treatment of Fungal Systemic Infection
by Mengjuan Cheng, Suke Liu, Mengsen Zhu, Mingchun Li and Qilin Yu
Molecules 2024, 29(19), 4547; https://doi.org/10.3390/molecules29194547 - 25 Sep 2024
Viewed by 583
Abstract
Life-threatening systemic fungal infections caused by Candida albicans are significant contributors to clinical mortality, particularly among cancer patients and immunosuppressed individuals. The evasion of the immune response facilitated by fungal surface components enables fungal pathogens to evade macrophage attacks and to establish successful [...] Read more.
Life-threatening systemic fungal infections caused by Candida albicans are significant contributors to clinical mortality, particularly among cancer patients and immunosuppressed individuals. The evasion of the immune response facilitated by fungal surface components enables fungal pathogens to evade macrophage attacks and to establish successful infections. This study developed a mesoporous silica nanoplatform, i.e., MSNP-EAP1Ab, which is composed of mesoporous silica nanoparticles grafted with the antibody of C. albicans surface adhesin Eap1. The activity of MSNP-EAP1Ab against C. albicans immune escape and infection was then evaluated by using the cell interaction model and the mouse systemic infection model. During interaction between C. albicans cells and macrophages, MSNP-EAP1Ab significantly inhibited fungal immune escape, leading to the enhanced phagocytosis of fungal cells by macrophages, with phagocytosis rates increasing from less than 8% to 14%. Furthermore, after treatment of the C. albicans-infected mice, MSNP-EAP1Ab drastically prolonged the mouse survival time and decreased the kidney fungal burden from >30,0000 CFU/g kidney to <100 CFU/g kidney, indicating the rapid recognition and killing of the pathogens by immune cells. Moreover, MSNP-EAP1Ab attenuated kidney tissue inflammation, with remarkable attenuation of renal immune cell accumulation. This study presents an innovative nanoplatform that targets the C. albicans adhesin, offering a promising approach for combatting systemic fungal infections. Full article
(This article belongs to the Special Issue Chemical Biology of Antimicrobial Resistance, 2nd Edition)
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