Antibiotic resistance (AR) remains a leading health challenge, affecting millions of the global population, creating economic burdens, and is responsible for most disease-related morbidity and mortality worldwide. It is characterized by the ability of pathogenic microorganisms to evade the pharmacological actions of antibiotics, and this occurs incessantly through multi-faceted, complex, and dynamic pathways. Relevant drug-resistant and multi-drug-resistant (MDR) microorganisms pose clinical challenges in the treatment of microbial infections by evolving AR-inclined pathomechanisms. Notably, these include modifications of cellular targets, genetic variability encoding, formation of biofilms and inaccessible sites for drugs, and catalytic metabolic destruction of antibiotics. Importantly, the unpleasant AR events affect all currently available antibiotic classes, including strong types such as cephalosporins, carbapenems, β-lactams, fluoroquinolones, and glycopeptide antibiotics, even in combined forms. Moreover, the mechanisms of AR development are mostly facilitated through the action of defensive macromolecules and enzymes produced by pathogens, such as the extended-spectrum β-lactamases (ESBL) produced by Enterobacteriaceae. These factors underscore the imperative need for the development of new antibiotics with enhanced efficacy through effective inhibitory mechanisms on AR-mediated organisms, enzymes, and pathways.

This research topic aims to explore emerging therapeutic strategies targeting bacterial proteins to combat antibiotic resistance. The main objectives include understanding the mechanisms of AR development, investigating the structural biology of AR-mediated macromolecules, and designing new antimicrobial agents. Specific questions to be addressed include: What are the key pathways and enzymes involved in AR? How can new antimicrobial agents be designed to effectively inhibit these pathways? What are the pharmacodynamics, pharmacokinetics, and toxicity profiles of these new agents?

To gather further insights into combating antibiotic resistance, we welcome articles addressing, but not limited to, the following themes:
- Studies on mechanisms of AR development
- Structural biology of AR-mediated macromolecules (proteins and enzymes), bioinformatics, and in silico studies
- Design and development of new antimicrobial agents
- Inhibition of pathogenic bacteria and fungi, AR-related proteins/enzymes, and pathways
- Reports on chemically characterized natural products and synthetic compounds with antimicrobial potential (GC-MS, NMR, HPLC, LC-MS, and FTIR characterization techniques are acceptable)
- Antimicrobial peptides and drug delivery
- Nutrition, immune system, and AR
- Pre-clinical in vitro and in vivo antimicrobial experiments
- Evolution of ESBLs and other defensive bacterial enzymes
- Pharmacodynamics, pharmacokinetics, and toxicity of new and existing antibiotics
- Antimicrobial studies of existing drugs and their formulations, including complexes, conjugates, and nanostructures
- Toxicity of existing and emerging antimicrobial agents
- Eubiosis and microbiota
- Repurposable drugs as potential antibiotics

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Frontiers in Antibiotics

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