Search Results (21)

Superficial mycoses (dermatomycoses) are a growing healthcare concern due to antifungal resistance, particularly among aging and immunocompromised populations. Multiple efforts are underway to develop novel antifungals, including discovering new compounds with known or new mechanisms of action, extending indications or repurposing existing medications, and utilizing vaccination and nanotechnology platforms. Herein, we conducted a scoping review of novel antifungals for the treatment of dermatomycoses. An electronic literature search restricted to the past 10 years was performed in January 2026 using PubMed and Embase (Ovid). Olorofim and ME1111 represent novel drug classes that target intracellular metabolism. New agents belonging to the azole class demonstrate reduced drug–drug interactions (oteseconazole), a broader antifungal spectrum (voriconazole), and reduced pharmacokinetic complexity (fosravuconazole, super-bioavailable itraconazole). Other investigational compounds include allicin, a phytocompound, and miltefosine, a repurposed antileishmanial drug. Based on our current understanding of dermatophyte immunity, antimicrobial peptides and vaccines targeting virulence factors (e.g., subtilisins) represent novel strategies. Nanotechnology platforms also show promise in introducing new antifungal agents (e.g., metal nanoparticles, nitric oxide-releasing nanoparticles), as well as developing topical formulations to enhance the bioavailability and safety profiles of existing antifungals (amphotericin B, ketoconazole, voriconazole). Full article

Iron is an essential micronutrient for nearly all microorganisms, yet its bioavailability is severely limited in most environments. To overcome this restriction, microorganisms produce siderophores, high-affinity iron-chelating molecules that play pivotal roles in microbial iron homeostasis, interspecies competition, and host–pathogen interactions. Despite extensive research, current understanding of siderophore biosynthetic and regulatory diversity remains largely limited to specific models, with comprehensive cross-taxonomic frameworks only beginning to emerge. This review systematically integrates recent advances in the genetic and biochemical foundations of microbial siderophore production, focusing on the two major biosynthetic pathways: nonribosomal peptide synthetase (NRPS)-dependent and NRPS-independent synthetase (NIS). We further elaborate on the diverse transport systems in Gram-negative and Gram-positive bacteria, as well as fungi, alongside the iron-responsive regulators (e.g., Fur) and gene clusters that coordinate iron uptake and utilization. Beyond physiological mechanisms, we discuss how these insights inform emerging applications of siderophores across multiple fields: in medicine, enabling “Trojan horse” antimicrobial strategies; in agriculture, enhancing plant iron uptake and serving as biocontrol agents; in environmental remediation, facilitating heavy-metal detoxification; and in biosensing, acting as selective probes for metals and pathogens. By bridging fundamental mechanisms with practical applications, this review aims to provide an integrative perspective for future exploration of microbial iron homeostasis and its biotechnological potential. Full article

Histatins are histidine-rich antimicrobial peptides present in human saliva, with histatin 5 (Hst5) demonstrating the most potent antifungal activity. Previous studies have linked the antifungal properties of histatins, particularly those against Candida species, to their ability to bind metal ions such as Cu(II) and Zn(II). While the antimicrobial activity of some histatins is well established, the impact of metal ion coordination on this activity remains an area of ongoing investigation. This study focuses on histatin 8 (Hst8), a less-explored member of the histatin family, and compares its metal-binding and antimicrobial properties to those of Hst5. Using isothermal titration microcalorimetry (ITC), we examined the interactions of Hst8 with Cu(II), Zn(II), and Ni(II) ions and evaluated its antimicrobial activity against Escherichia coli, Staphylococcus aureus and two Candida albicans strains. Our findings revealed significant differences in copper and zinc binding between Hst5 and Hst8, with both peptides exhibiting distinct antifungal profiles. Interestingly, it has been shown that copper ions bind to Hst5 in a distinctly different manner than to Hst8. Hst5 exhibits two binding sites with dissociation constants (K_DITC) of 0.2 µM and 14.8 µM, whereas Hst8 has only one set of binding sites with a K_DITC of 12.3 µM. These results highlight the potential role of metal ion coordination in modulating the antimicrobial efficacy of histatins, providing further insight into their therapeutic potential. Full article

Rare-earth oxide (REO) nanoparticles (NPs)—such as cerium (CeO₂), samarium (Sm₂O₃), neodymium (Nd₂O₃), terbium (Tb₄O₇), and praseodymium (Pr₂O₃)—have demonstrated strong antimicrobial activity against multidrug-resistant bacteria. Their effectiveness is attributed to unique physicochemical properties, including oxygen vacancies and redox cycling, which facilitate the generation of reactive oxygen species (ROS) that damage microbial membranes and biomolecules. Additionally, electrostatic interactions with microbial surfaces and sustained ion release contribute to membrane disruption and long-term antimicrobial effects. REOs also inhibit bacterial enzymes, DNA, and protein synthesis, providing broad-spectrum activity against Gram-positive, Gram-negative, and fungal pathogens. However, dose-dependent cytotoxicity to mammalian cells—primarily due to excessive ROS generation—and nanoparticle aggregation in biological media remain challenges. Surface functionalization with polymers, peptides, or metal dopants (e.g., Ag, Zn, and Cu) can mitigate cytotoxicity and enhance selectivity. Scalable and sustainable synthesis remains a challenge due to high synthesis costs and scalability issues in industrial production. Green and biogenic routes using plant or microbial extracts can produce REOs at lower cost and with improved safety. Advanced continuous flow and microwave-assisted synthesis offer improved particle uniformity and production yields. Biomedical applications include antimicrobial coatings, wound dressings, and hybrid nanozyme systems for oxidative disinfection. However, comprehensive and intensive toxicological evaluations, along with regulatory frameworks, are required before clinical deployment. Full article

It remains an open question whether violets use universal mechanisms, such as the production of metallothioneins, phytochelatins, and organic acids and/or rely on specific mechanisms like the production of antimicrobial cyclic peptides (cyclotides) for heavy metal tolerance. To contribute to the understanding of the role of cyclotides, we used seed-derived plants from metallicolous (M) and non-metallicolous (NM) populations of Viola tricolor, a pseudometallophyte tolerant to Zn and Pb. Eight- to ten-week-old plants were treated with 1000 μM of Zn or Pb for 3 or 7 days and subsequently measured for cyclotides and heavy metal content using MALDI-MS and Atomic Absorption Spectrometry (AAS), respectively. Individuals from the M population accumulated a similar amount of Zn but occasionally more Pb in comparison with the NM population. Of the 18 different cyclotides included in the analysis, some showed statistically significant changes under the heavy metal treatment. In general, a decrease was observed in the M population, whereas an increase was observed in the NM population (except for the 3-day treatment with Zn). The day of treatment and dose of metal and their interaction played a crucial role in the explained variance for cyclotides produced by the M individuals but not for the NM plants. This unravels the importance of this antimicrobial compound in heavy metal tolerance and indicates that, in V. tricolor, cyclotides are involved in heavy metal tolerance, but specimens from two populations have developed different strategies and tolerance mechanisms involving cyclotides to mitigate heavy metal stress. Full article

Copper-chelated chitosan microgels were investigated as an immobilized metal affinity chromatography (IMAC) phase for peptide separation. The copper-crosslinked chitosan beads were shown to strongly interact with a range of amino acids, in a wide range of pH and saline conditions. The beads exhibited an affinity that seemed to depend on the isoelectric point of the amino acid, with the extent of uptake increasing with decreasing isoelectric point. This selective interaction with anionic amino acids resulted in a significant relative enrichment of the supernatant solution in cationic amino acids. The beads were then studied as a novel fractionation system for complex milk hydrolysates. The copper chitosan beads selectively removed larger peptides from the hydrolysate aqueous solution, yielding a solution relatively enriched in medium and smaller peptides, which was characterized both quantitatively and qualitatively by size exclusion chromatography (SEC). Liquid chromatography–mass spectrometry (LCMS) work provided comprehensive data on a peptide sequence level and showed that a depletion of the anionic peptides by the beads resulted in a relative enrichment of the cationic peptides in the supernatant solution. It could be concluded that after fractionation a dramatic relative enrichment in respect to small- and medium-sized cationic peptides in the solution, characteristics that have been linked to bioactivities, such as anti-microbial and cell-penetrating properties. The results demonstrate the use of the chitosan copper gel bead system in lab scale fractionation of complex hydrolysate mixtures, with the potential to enhance milk hydrolysate bioactivity. Full article

Antimicrobial resistance threatens the effective prevention and treatment of an increasingly broad spectrum of infections caused by pathogenic microorganisms. This pressing challenge has intensified the search for alternative antibiotics with new pharmacological properties. Due to the chemical synergy between the biological activity of antimicrobial peptides (AMPs) and the different modes of action, catalytic properties, and redox chemistry of metal complexes, metallopeptides have emerged in recent years as an alternative to conventional antibiotics. In the present investigation, peptide ligands conjugated with 5-carboxy-1,10-phenanthroline (Phen) were prepared by solid-phase peptide synthesis (SPPS), and the corresponding copper(II) metallopeptides, Cu-PhenKG and Cu-PhenRG (where K = lysine, R = arginine, and G = glycine), were synthesized and characterized. The antimicrobial activities of these compounds toward Gram-positive and Gram-negative bacteria, evaluated by the broth microdilution technique, indicate that the metal center in the metallopeptides increases the antimicrobial activity of the complexes against the conjugated peptide ligands. Minimum inhibitory concentration (MIC) values of 0.5 μg/mL for S. aureus with the Cu-PhenKG complex and 0.63 μg/mL for S. typhimurium with the Cu-PhenRG complex were obtained. The MIC values found for the conjugated peptides in all microorganisms tested were greater than 1.5 μg/mL. The interactions of the conjugated peptides and their metallopeptides with plasmid DNA were evaluated by agarose gel electrophoresis. Alterations on the replication machinery were also studied by polymerase chain reaction (PCR). The results indicate that the complexes interact efficiently with pBR322 DNA from E. coli, delaying the band shift. Furthermore, the resulting DNA–metallopeptide complex is not a useful template DNA because it inhibits PCR, since no PCR product was detected. Finally, molecular dynamics and molecular docking simulations were performed to better understand the interactions of the obtained compounds with DNA. The Cu-PhenRG complex shows a significantly higher number of polar interactions with DNA, suggesting a higher binding affinity with the biopolymer. Full article

Peptides, both natural and synthetic, are well suited for a wide range of purposes and offer versatile applications in different fields such as biocatalysts, injectable hydrogels, tumor treatment, and drug delivery. The research of the better part of the cited papers was conducted using various database platforms such as MetalPDB. The rising prominence of therapeutic peptides encompasses anticancer, antiviral, antimicrobial, and anti-neurodegenerative properties. The metals Na, K, Mg, Ca, Fe, Mn, Co, Cu, Zn, and Mo are ten of the twenty elements that are considered essential for life. Crucial for understanding the biological role of metals is the exploration of metal-bound proteins and peptides. Aside from essential metals, there are other non-essential metals that also interact biologically, exhibiting either therapeutic or toxic effects. Irregularities in metal binding contribute to diseases like Alzheimer’s, neurodegenerative disorders, Wilson’s, and Menkes disease. Certain metal complexes have potential applications as radiopharmaceuticals. The examination of these complexes was achieved by preforming UV–Vis, IR, EPR, NMR spectroscopy, and X-ray analysis. This summary, although unable to cover all of the studies in the field, offers a review of the ongoing experimentation and is a basis for new ideas, as well as strategies to explore and gain knowledge from the extensive realm of peptide-chelated metals and biotechnologies. Full article

The metal chelator PBT2 (5,7-dichloro-2-[(dimethylamino)methyl]-8-hydroxyquinoline) acts as a terdentate ligand capable of forming binary and ternary Cu²⁺ complexes. It was clinically trialed as an Alzheimer’s disease (AD) therapy but failed to progress beyond phase II. The β-amyloid (Aβ) peptide associated with AD was recently concluded to form a unique Cu(Aβ) complex that is inaccessible to PBT2. Herein, it is shown that the species ascribed to this binary Cu(Aβ) complex in fact corresponds to ternary Cu(PBT2)N_Im^Aβ complexes formed by the anchoring of Cu(PBT2) on imine nitrogen (N_Im) donors of His side chains. The primary site of ternary complex formation is His6, with a conditional stepwise formation constant at pH 7.4 ($K_c^{}$ [M⁻¹]) of log$K_{}^c$ = 6.4 ± 0.1, and a second site is supplied by His13 or His14 (log$K_{}^c$ = 4.4 ± 0.1). The stability of Cu(PBT2)N_Im^H13/14 is comparable with that of the simplest Cu(PBT2)N_Im complexes involving the N_Im coordination of free imidazole (log$K_{}^c$ = 4.22 ± 0.09) and histamine (log$K_{}^c$ = 4.00 ± 0.05). The 100-fold larger formation constant for Cu(PBT2)N_Im^H6 indicates that outer-sphere ligand–peptide interactions strongly stabilize its structure. Despite the relatively high stability of Cu(PBT2)N_Im^H6, PBT2 is a promiscuous chelator capable of forming a ternary Cu(PBT2)N_Im complex with any ligand containing an N_Im donor. These ligands include histamine, L-His, and ubiquitous His side chains of peptides and proteins in the extracellular milieu, whose combined effect should outweigh that of a single Cu(PBT2)N_Im^H6 complex regardless of its stability. We therefore conclude that PBT2 is capable of accessing Cu(Aβ) complexes with high stability but low specificity. The results have implications for future AD therapeutic strategies and understanding the role of PBT2 in the bulk transport of transition metal ions. Given the repurposing of PBT2 as a drug for breaking antibiotic resistance, ternary Cu(PBT2)N_Im and analogous Zn(PBT2)N_Im complexes may be relevant to its antimicrobial properties. Full article

Histidine and cysteine residues, with their imidazole and thiol moieties that deprotonate at approximately physiological pH values, are primary binding sites for Zn(II), Ni(II) and Fe(II) ions and are thus ubiquitous both in peptidic metallophores and in antimicrobial peptides that may use nutritional immunity as a way to limit pathogenicity during infection. We focus on metal complex solution equilibria of model sequences encompassing Cys–His and His–Cys motifs, showing that the position of histidine and cysteine residues in the sequence has a crucial impact on its coordination properties. CH and HC motifs occur as many as 411 times in the antimicrobial peptide database, while similar CC and HH regions are found 348 and 94 times, respectively. Complex stabilities increase in the series Fe(II) < Ni(II) < Zn(II), with Zn(II) complexes dominating at physiological pH, and Ni(II) ones—above pH 9. The stabilities of Zn(II) complexes with Ac-ACHA-NH₂ and Ac-AHCA-NH₂ are comparable, and a similar tendency is observed for Fe(II), while in the case of Ni(II), the order of Cys and His does matter—complexes in which the metal is anchored on the third Cys (Ac-AHCA-NH₂) are thermodynamically stronger than those where Cys is in position two (Ac-ACHA-NH₂) at basic pH, at which point amides start to take part in the binding. Cysteine residues are much better Zn(II)-anchoring sites than histidines; Zn(II) clearly prefers the Cys–Cys type of ligands to Cys–His and His–Cys ones. In the case of His- and Cys-containing peptides, non-binding residues may have an impact on the stability of Ni(II) complexes, most likely protecting the central Ni(II) atom from interacting with solvent molecules. Full article

Antimicrobial peptides (AMPs) are essential components of innate immunity across all species. AMPs have become the focus of attention in recent years, as scientists are addressing antibiotic resistance, a public health crisis that has reached epidemic proportions. This family of peptides represents a promising alternative to current antibiotics due to their broad-spectrum antimicrobial activity and tendency to avoid resistance development. A subfamily of AMPs interacts with metal ions to potentiate antimicrobial effectiveness, and, as such, they have been termed metalloAMPs. In this work, we review the scientific literature on metalloAMPs that enhance their antimicrobial efficacy when combined with the essential metal ion zinc(II). Beyond the role played by Zn(II) as a cofactor in different systems, it is well-known that this metal ion plays an important role in innate immunity. Here, we classify the different types of synergistic interactions between AMPs and Zn(II) into three distinct classes. By better understanding how each class of metalloAMPs uses Zn(II) to potentiate its activity, researchers can begin to exploit these interactions in the development of new antimicrobial agents and accelerate their use as therapeutics. Full article

Multidrug-resistant bacteria form serious problems in many areas, including medicine and the food industry. At the same time, great interest is shown in the transfer or enhancement of antimicrobial properties to various materials by modifying them with enzymes. The use of enzymes in biomaterials with antimicrobial properties is important because enzymes can be used as the main active components providing antimicrobial properties of functionalized composite biomaterials, or can serve as enhancers of the antimicrobial action of certain substances (antibiotics, antimicrobial peptides, metal nanoparticles, etc.) against cells of various microorganisms. Enzymes can simultaneously widen the spectrum of antimicrobial activity of biomaterials. This review presents the most promising enzymes recently used for the production of antibacterial materials, namely hydrolases and oxidoreductases. Computer modeling plays an important role in finding the most effective combinations between enzymes and antimicrobial compounds, revealing their possible interactions. The range of materials that can be functionalized using enzymes looks diverse. The physicochemical characteristics and functionalization methods of the materials have a significant impact on the activity of enzymes. In this context, fibrous materials are of particular interest. The purpose of this review is to analyze the current state of the art in this area. Full article

Antibiotic resistance demands innovative strategies and therapies. The pairs of antimicrobial peptides tested in this work show broad-spectrum synergy and are capable of interacting with diverse bacterial membranes. In most cases, the ATCUN motif enhanced the activity of peptides tested in combination. Our studies also show CP10A to be a multifaceted peptide, displaying both cell membrane and intracellular activity and acting as a chameleon, improving the activity of other peptides as needed. The results of the synergy experiments demonstrate the importance of varied modes of action and how these changes can affect the ability to combat pathogens, while also illustrating the value of the metal-binding domain in enhancing the activity of antimicrobial peptides in combination. Full article

Peptide-based materials provide a versatile platform for sensing and ion sequestration since peptides are endowed with stimuli-responsive properties. The mechanism of molecular sensing is often based on peptide structural changes (or switching), caused by the binding of the target molecule. One scope of sensing applications is the selection of a specific analyte, which may be achieved by adjusting the structure of the peptide binding site. Therefore, exact knowledge of peptide properties and 3D-structure in the ‘switched’ state is desirable for tuning the detection and for further molecular construction. Hence, here we demonstrate the performance of Electron Paramagnetic Resonance (EPR) spectroscopy in the identification of metal ion binding by the antimicrobial peptide trichogin GA IV. Na(I), Ca(II), and Cu(II) ions were probed as analytes to evaluate the impact of coordination number, ionic radii, and charge. Conclusions drawn by EPR are in line with literature data, where other spectroscopic techniques were exploited to study peptide-ion interactions for trichogin GA IV, and the structural switch from an extended helix to a hairpin structure, wrapped around the metal ion upon binding of divalent cations was proposed. Full article

Conducting polymers, mainly polyaniline (PANI) and polypyrrole (PPY) with positive charges bind to the negatively charged bacterial membrane to interfere with bacterial activities. After this initial electrostatic adherence, the conducting polymers might partially penetrate the bacterial membrane and interact with other intracellular biomolecules. Conducting polymers can form polymer composites with metal, metal oxides, and nanoscale carbon materials as a new class of antimicrobial agents with enhanced antimicrobial properties. The accumulation of elevated oxygen reactive species (ROS) from composites of polymers-metal nanoparticles has harmful effects and induces cell death. Among such ROS, the hydroxyl radical with one unpaired electron in the structure is most effective as it can oxidize any bacterial biomolecules, leading to cell death. Future endeavors should focus on the combination of conducting polymers and their composites with antibiotics, small peptides, and natural molecules with antimicrobial properties. Such arsenals with low cytotoxicity are expected to eradicate the ESKAPE pathogens: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. Full article