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Novel Antibacterial Drugs: Discovery, Synthesis and Design

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pharmacology".

Deadline for manuscript submissions: closed (31 July 2023) | Viewed by 3021

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Toxinology Laboratory, Department of Physiological Sciences, Institute of Biology, University of Brasilia, Brasilia 70.910-900, Brazil
Interests: amphibians; peptide chemistry; antimicrobial peptides; peptide synthesis; peptide analogues; neurotoxic peptides; scorpions
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Special Issue Information

Dear Colleagues, 

Random mutations cause genetic variations in microorganisms, so the emergence of antimicrobial resistance is a natural evolutionary process; however, external selective pressures, such as exposure to antimicrobial agents in healthcare, agriculture, and the environment, can accelerate the dissemination of these genes. Antimicrobial resistance threatens, at alarming levels, the limited treatment options available and portends one of the greatest global public health crises. There are already reports of pathogens endowed with resistance to multiple drugs (MDR) that are considered untreatable, a particularly worrying situation in the context of nosocomial infections and one that has worsened during the COVID-19 pandemic, due to the significant increase in the use of antibiotics during this period. The scenario of resistance has been shaped by a combination of factors, such as the inappropriate use of antibiotics in clinical practice and the livestock industry, the use of bactericides and fungicides in agriculture, and even environmental pollution. This situation becomes especially urgent when one notices the lack of new antibiotics under development. The latest discovery of a new antibiotic class that has reached the market was back in 1987, showing a large gap in the evolution of antimicrobial therapies, which remains until today. In view of this situation, the search for new antibacterial compounds becomes urgent, and this Special Issue will accept original research articles and reviews that highlight the discovery, synthesis, and design of novel antibacterial agents, essential initiatives through which to limit the dissemination of multidrug-resistant microorganisms and ensure the adequate treatment of exposed populations, preventing associated human losses.

Prof. Dr. Mariana S. Castro
Guest Editor

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Keywords

  • antibacterial agents
  • bacterial infections
  • discovery
  • rational design
  • small molecules
  • peptides
  • peptidomimetics
  • antibacterial drug targets
  • structure–activity relationship

Published Papers (2 papers)

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Research

18 pages, 15621 KiB  
Article
Optimization of Antibacterial Activity and Biosafety through Ultrashort Peptide/Cyclodextrin Inclusion Complexes
by Hang Liu, Lin Wang and Chen Yao
Int. J. Mol. Sci. 2023, 24(19), 14801; https://doi.org/10.3390/ijms241914801 - 30 Sep 2023
Cited by 1 | Viewed by 1145
Abstract
Engineered ultrashort peptides, serving as an alternative to natural antimicrobial peptides, offer benefits of simple and modifiable structures, as well as ease of assembly. Achieving excellent antibacterial performance and favorable biocompatibility through structural optimization remains essential for further applications. In this study, we [...] Read more.
Engineered ultrashort peptides, serving as an alternative to natural antimicrobial peptides, offer benefits of simple and modifiable structures, as well as ease of assembly. Achieving excellent antibacterial performance and favorable biocompatibility through structural optimization remains essential for further applications. In this study, we assembled lipoic acid (LA)–modified tripeptide RWR (LA–RWR) with β–cyclodextrin (β–CD) to form nano–inclusion complexes. The free cationic tripeptide region in the nano–inclusion complex provided high antibacterial activity, while β–CD enhanced its biocompatibility. Compared with peptides (LA–RWR, LA–RWR–phenethylamine) alone, inclusion complexes exhibited lower minimum inhibitory concentrations/minimum bactericidal concentrations (MICs/MBCs) against typical Gram–negative/Gram–positive bacteria and fungi, along with improved planktonic killing kinetics and antibiofilm efficiency. The antibacterial mechanism of the nano–inclusion complexes was confirmed through depolarization experiments, outer membrane permeability experiments, and confocal laser scanning microscopy observations. Furthermore, biological evaluations indicated that the hemolysis rate of the inclusion complexes decreased to half or even lower at high concentrations, and cell viability was superior to that of the non–included peptides. Preliminary in vivo studies suggested that the inclusion complexes, optimized for antibacterial activity and biosafety, could be used as promising antibacterial agents for potential applications. Full article
(This article belongs to the Special Issue Novel Antibacterial Drugs: Discovery, Synthesis and Design)
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15 pages, 3548 KiB  
Article
Identification and Characterization of RK22, a Novel Antimicrobial Peptide from Hirudinaria manillensis against Methicillin Resistant Staphylococcus aureus
by Xiaoyu Lu, Min Yang, Shengwen Zhou, Shuo Yang, Xiran Chen, Mehwish Khalid, Kexin Wang, Yaqun Fang, Chaoming Wang, Ren Lai and Zilei Duan
Int. J. Mol. Sci. 2023, 24(17), 13453; https://doi.org/10.3390/ijms241713453 - 30 Aug 2023
Cited by 1 | Viewed by 1614
Abstract
Staphylococcus aureus (S. aureus) infections are a leading cause of morbidity and mortality, which are compounded by drug resistance. By manipulating the coagulation system, S. aureus gains a significant advantage over host defense mechanisms, with hypercoagulation induced by S. aureus potentially [...] Read more.
Staphylococcus aureus (S. aureus) infections are a leading cause of morbidity and mortality, which are compounded by drug resistance. By manipulating the coagulation system, S. aureus gains a significant advantage over host defense mechanisms, with hypercoagulation induced by S. aureus potentially aggravating infectious diseases. Recently, we and other researchers identified that a higher level of LL-37, one endogenous antimicrobial peptide with a significant killing effect on S. aureus infection, resulted in thrombosis formation through the induction of platelet activation and potentiation of the coagulation factor enzymatic activity. In the current study, we identified a novel antimicrobial peptide (RK22) from the salivary gland transcriptome of Hirudinaria manillensis (H. manillensis) through bioinformatic analysis, and then synthesized it, which exhibited good antimicrobial activity against S. aureus, including a clinically resistant strain with a minimal inhibitory concentration (MIC) of 6.25 μg/mL. The RK22 peptide rapidly killed S. aureus by inhibiting biofilm formation and promoting biofilm eradication, with good plasma stability, negligible cytotoxicity, minimal hemolytic activity, and no significant promotion of the coagulation system. Notably, administration of RK22 significantly inhibited S. aureus infection and the clinically resistant strain in vivo. Thus, these findings highlight the potential of RK22 as an ideal treatment candidate against S. aureus infection. Full article
(This article belongs to the Special Issue Novel Antibacterial Drugs: Discovery, Synthesis and Design)
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