Membrane-Active Antibiotics Affect Domains in Bacterial Membranes as the First Step of Their Activity.

The need to combat antimicrobial resistance is becoming more and more pressing. Here we investigate the working mechanism of a small cationic agent, N-alkylamide 3d, by conventional and high-speed atomic force microscopy. We show that N-alkylamide 3d interacts with the membrane of Staphylococcus aureus, where it changes the organization and dynamics of lipid domains. After this initial step, supramolecular structures of the antimicrobial agent attach on top of the affected membrane gradually, covering it entirely. These results demonstrate that lateral domains in the bacterial membranes might be affected by small antimicrobial agents more often than anticipated. At the same time, we show a new dual-step activity of N-alkylamide 3d that not only destroys the lateral membrane organization but also effectively covers the whole membrane with aggregates. This final step could render the membrane inaccessible from the outside and possibly prevent signaling and waste disposal of living bacteria.

Synthesis and characterization of new acid-functionalized porphyrins displaying antimicrobial activity against gram positive bacteria, yeasts and filamentous fungi with or without ultra-high irradiance.

The antimicrobial activity of new acid-functionalized porphyrins, with or without ultra-high irradiance, was investigated. Antibacterial efficacy was evaluated against Staphylococcus aureus (methicillin-resistant or methicillin-sensitive strains) and antifungal efficacy was evaluated against the yeast Candida albicans and the filamentous fungi Aspergillus fumigatus. Overall, the porphyrins tested are more effective against S. aureus. The best results were obtained with zinc diacid porphyrins 4 and 5 after only 3 min of ultra-high irradiation (500 mW/cm2, 405 nm), demonstrating that acid-functionalized porphyrins are promising as novel antimicrobial drugs for surface disinfection.

Synthesis of zero valent copper/iron nanoparticles using Piper betle leaves for the removal of pharmaceutical contaminant atorvastatin.

In this study, bimetallic Cu-Fe nanoparticles were synthesized using the green approach with Piper betle leaves, and the removal efficiency of one of the pharmaceutical compounds, Atorvastatin, was investigated. UV, SEM, FTIR, EDAX, particle size, and zeta potential measurements were used to confirm nanoparticle fabrication. The removal efficiency of Atorvastatin (10 mg/L) by bimetallic Cu-Fe nanoparticles was 67% with a contact time of 30 min at pH 4, the adsorbent dosage of 0.2 g/L, and stirring at 100 rpm. Piper betle bimetallic Cu-Fe nanoparticles have demonstrated excellent stability, reusability, and durability, even after being reused five times. Furthermore, the synthesized bimetallic Cu-Fe nanoparticles demonstrated remarkable antimicrobial properties against gram-negative strains such as Escherichia coli and Klebsiella pneumoniae, gram-positive strains such as Staphylococcus aureus and Bacillus subtilis, and fungi such as Aspergillus niger. In addition, the antioxidant properties of the synthesized bimetallic Cu-Fe nanoparticles were assessed using the DPPH radical scavenging assay. The results indicated that the nanoparticles had good antioxidant activity. Thus, using Piper betle extract to make Cu-Fe nanoparticles made the procedure less expensive, chemical-free, and environmentally friendly, and the synthesized bimetallic Cu-Fe nanoparticles helped remove the pharmaceutical compound Atorvastatin from wastewater.

Cryptocarya moschata extract decreases single and mixed biofilms on acrylic resins.

OBJECTIVE: This study proposed to assess the effect of Cryptocarya moschata extract on single and mixed biofilms formed on denture base and reline acrylic resin. MATERIALS AND METHODS: Single and mixed biofilms of Candida albicans and Streptococcus mutans were formed on the samples and treated with C. moschata extract; Nystatin solution at 100,000 IU/mL or Penicillin antibiotic solution at 100,000 IU/mL; or PBS solution. Antimicrobial activity was analyzed by counting colony-forming units, metabolism assay, assessment of protein components of the biofilm matrix, and of cell viability using confocal laser scanning microscopy (CLSM). Data were submitted to ANOVA and Tukey's post-test (α = 0.05). RESULTS: Cryptocarya moschata extract reduced cell viability of C. albicans and S. mutans single and mixed biofilms formed on samples. For all types of biofilms in the C. moschata group, there was a log reduction of the biofilm, proven by the Alamar Blue assay. Analyzing the extracellular matrix protein components, groups treated with the extract exhibited a lower level of fluorescence compared to the PBS groups. Reduction in thickness biofilm and viable cells was perceptible in the C. moschata group when assessing through CLSM. CONCLUSION: Cryptocarya moschata extract reduced the single and mixed biofilms of C. albicans and S. mutans on acrylic resins.

Recent Advances in Antibacterial Coatings to Combat Orthopedic Implant-Associated Infections.

Implant-associated infections (IAIs) represent a major health burden due to the complex structural features of biofilms and their inherent tolerance to antimicrobial agents and the immune system. Thus, the viable options to eradicate biofilms embedded on medical implants are surgical operations and long-term and repeated antibiotic courses. Recent years have witnessed a growing interest in the development of robust and reliable strategies for prevention and treatment of IAIs. In particular, it seems promising to develop materials with anti-biofouling and antibacterial properties for combating IAIs on implants. In this contribution, we exclusively focus on recent advances in the development of modified and functionalized implant surfaces for inhibiting bacterial attachment and eventually biofilm formation on orthopedic implants. Further, we highlight recent progress in the development of antibacterial coatings (including self-assembled nanocoatings) for preventing biofilm formation on orthopedic implants. Among the recently introduced approaches for development of efficient and durable antibacterial coatings, we focus on the use of safe and biocompatible materials with excellent antibacterial activities for local delivery of combinatorial antimicrobial agents for preventing and treating IAIs and overcoming antimicrobial resistance.

Emycin-E purified from Streptomyces sp. RG1011 from Himalayan soil has antibiofilm activity against Staphylococcus aureus.

BACKGROUND: Staphylococcus aureus is an opportunistic pathogen that causes deadly infections in human as well as animals. The intricate network of virulence factors and biofilms are the major hindrance for the antibiotics in the successful treatment of the infection. The aim of this study is to isolate, identify and characterize natural antimicrobial agent against S. aureus from natural resources. METHODS: Himalayan soils were subjected to primary, secondary and tertiary screening to isolate soil Actinobacteria. Identification and characterization of the isolate was done by various biochemical assays and 16s rDNA sequencing. Partial purification of the potent antimicrobial agent was done by n-butanol from the culture supernatant, TLC and HPLC were performed to purify the active component and subjected to FTIR and ESI-MS analysis. RESULTS: The potent isolate RM-1(13) was confirmed as Streptomyces griseus strain RG1011 (NCBI accession no: 0M780275) by biochemical and molecular analysis. The partially purified antimicrobial agent was active against various Gram-positive and Gram-negative pathogens. The active component was purified by HPLC and identified as Emycin-E by ESI-MS analysis. The Emycin-E has calculated MIC of 0.31 µg/ml against S. aureus ATCC 25923. Emycin-E inhibits the biofilm formation of S. aureus in in vitro microtiter plate assay. CONCLUSIONS: The identified antimicrobial agent was found active against various Gram-positive and Gram-negative pathogens. We have successfully identified the active compound as Emycin-E by FTIR and ESI-MS analysis. Our study suggests the role of Emycin-E in the inhibition of biofilm formation in S. aureus.

Exposure to systemic antibiotics in outpatient care and the risk of multiple sclerosis.

BACKGROUND: Infections, early life exposures and the microbiome have been associated with the aetiology of multiple sclerosis (MS). Data on any possible roles of antibiotics is scarce and conflicting. OBJECTIVE: The objective of this study was to investigate associations between outpatient systemic antibiotic exposure and the risk of MS in a nationwide case-control setting. METHODS: Patients with MS were identified from the nation MS registry and their exposure to antibiotics was compared with that of persons without MS, provided by the national census authority. Antibiotic exposure was investigated using the national prescription database and analyzed by Anatomical Therapeutic Chemical (ATC) category. RESULTS: Among the 1830 patients with MS and 12765 control persons, there were no associations between exposure to antibiotics in childhood (5-9 years) or adolescence (10-19 years) and the subsequent risk of MS. There was also no association between antibiotic exposure 1-6 years before disease onset and the risk of MS, save for exposure to fluoroquinolones in women (odds ratio: 1.28; 95% confidence interval: 1.03, 1.60; p = 0.028) which is probably associated with the increased infection burden in the MS prodrome. CONCLUSION: Use of systemic prescription antibiotics was not associated with subsequent MS risk.

Abrading-Induced Breakdown of Ag Nanoparticles into Atomically Dispersed Ag for Enhancing Antimicrobial Performance.

Silver is among the most essential antimicrobial agents. Increasing the efficacy of silver-based antimicrobial materials will reduce operating costs. Herein, we show that mechanical abrading causes atomization of Ag nanoparticles (AgNPs) into atomically dispersed Ag (AgSAs) on the surfaces of an oxide-mineral support, which eventually boosts the antibacterial efficacy considerably. This approach is straightforward, scalable, and applicable to a wide range of oxide-mineral supports; additionally, it does not require any chemical additives and operates under ambient conditions. The obtained AgSAs-loaded γ-Al2O3 inactivated Escherichia coli (E. coli) five times as fast as the original AgNPs-loaded γ-Al2O3. It can be utilized over 10 runs with minimal efficiency loss. The structural characterizations indicate that AgSAs exhibit a nominal charge of 0 and are anchored at the doubly bridging OH on the γ-Al2O3 surfaces. Mechanism studies demonstrate that AgSAs, like AgNPs, damage bacterial cell wall integrity, but they release Ag+ and superoxide substantially faster. This work not only provides a simple method for manufacturing AgSAs-based materials but also shows that AgSAs have better antibacterial properties than the AgNPs counterpart.

Biochemical Characterizations of the Putative Amidase Endolysin Ecd18980 Catalytic Domain from Clostridioides difficile.

Clostridioides difficile is the major causative pathogen of pseudomembranous colitis, and novel antimicrobial agents are required for treatment. Phage-derived endolysins exhibiting species-specific lytic activity have potential as novel antimicrobial agents. We surveyed the genome of C. difficile strain 630 and identified a gene encoding an endolysin, Ecd18980, which has an amidase_3 domain at the N-terminus but unknown C-terminal domain. The genes encoding Ecd18980 and its catalytic domain (Ecd18980CD) were cloned and expressed in Escherichia coli as N-terminal histidine-tagged proteins. These purified proteins showed lytic activity against C. difficile. Ecd18980CD showed higher lytic activity than the wild-type enzyme and near-specific lytic activity against C. difficile. This species specificity is thought to depend on substrate cleavage activity rather than binding. We also characterized the biochemical properties of Ecd18980CD, including optimal pH, salt concentration, and thermal stability.

A Comparative Study of the Inhibitory Action of Berberine Derivatives on the Recombinant Protein FtsZ of E. coli.

Medicinal plants belonging to the genus Berberis may be considered an interesting source of drugs to counteract the problem of antimicrobial multiresistance. The important properties associated with this genus are mainly due to the presence of berberine, an alkaloid with a benzyltetrahydroisoquinoline structure. Berberine is active against both Gram-negative and Gram-positive bacteria, influencing DNA duplication, RNA transcription, protein synthesis, and the integrity of the cell surface structure. Countless studies have shown the enhancement of these beneficial effects following the synthesis of different berberine analogues. Recently, a possible interaction between berberine derivatives and the FtsZ protein was predicted through molecular docking simulations. FtsZ is a highly conserved protein essential for the first step of cell division in bacteria. The importance of FtsZ for the growth of numerous bacterial species and its high conservation make it a perfect candidate for the development of broad-spectrum inhibitors. In this work, we investigate the inhibition mechanisms of the recombinant FtsZ of Escherichia coli by different N-arylmethyl benzodioxolethylamines as berberine simplified analogues appropriately designed to evaluate the effect of structural changes on the interaction with the enzyme. All the compounds determine the inhibition of FtsZ GTPase activity by different mechanisms. The tertiary amine 1c proved to be the best competitive inhibitor, as it causes a remarkable increase in FtsZ Km (at 40 µM) and a drastic reduction in its assembly capabilities. Moreover, a fluorescence spectroscopic analysis carried out on 1c demonstrated its strong interaction with FtsZ (Kd = 26.6 nM). The in vitro results were in agreement with docking simulation studies.

Toxicity Mechanisms of Copper Nanoparticles and Copper Surfaces on Bacterial Cells and Viruses.

Copper is a metal historically used to prevent infections. One of the most relevant challenges in modern society are infectious disease outbreaks, where copper-based technologies can play a significant role. Currently, copper nanoparticles and surfaces are the most common antimicrobial copper-based technologies. Despite the widespread use of copper on nanoparticles and surfaces, the toxicity mechanism(s) explaining their unique antimicrobial properties are not entirely known. In general, toxicity effects described in bacteria and fungi involve the rupture of membranes, accumulation of ions inside the cell, protein inactivation, and DNA damage. A few studies have associated Cu-toxicity with ROS production and genetic material degradation in viruses. Therefore, understanding the mechanisms of the toxicity of copper nanoparticles and surfaces will contribute to developing and implementing efficient antimicrobial technologies to combat old and new infectious agents that can lead to disease outbreaks such as COVID-19. This review summarizes the current knowledge regarding the microbial toxicity of copper nanoparticles and surfaces and the gaps in this knowledge. In addition, we discuss potential applications derived from discovering new elements of copper toxicity, such as using different molecules or modifications to potentiate toxicity or antimicrobial specificity.

Pharmacokinetics and tissue distribution of florfenicol and florfenicol amine in snubnose pompano (Trachinotus blochii) following oral administration.

The present study reports the comparative pharmacokinetic profiles of florfenicol and its metabolite (florfenicol amine, FFA) in Trachinotus blochii under tropical marine conditions (salinity: 35 ± 1.4‰; temperature: 28.8 ± 0.54 °C) following a single in-feed oral administration of the recommended dose (15 mg/Kg). Furthermore, the study investigated the distribution of these two compounds in nine different tissues. The maximum florfenicol concentrations (Cmax) in plasma and tissues were observed within five hours (Tmax), except for bile. The Cmax ranged from 572 to 1954 ng/g or ml and was in the intestine > bile > muscle + skin > liver > gill = heart > plasma > kidney = spleen. The elimination half-life of FFC was significantly slower in the bile (38.25 ± 4.46 h). The AUC tissue/plasma was highest for bile (3.77 ± 0.22), followed by intestine > muscle + skin > heart > liver > kidney = gill = spleen. Tmax and t1/2ß were slower, and Cmax was lower for FFA than florfenicol in all tissues except Cmax of the kidney and bile. FFA t1/2ß was exceptionally slower in the kidney (46.01 ± 8.2 h). Interestingly, reaching an apparent distribution rate of > 0.5 was comparatively faster in the kidney, liver, and gills than in other tissues. The highest apparent metabolic rate was in the kidney (0.95 ± 0.01) and the lowest in plasma (0.41 ± 0.01). The generated data can be applied for formulating efficient therapeutic protocols in T. blochii, a promising mariculture species.

An Antimicrobial Peptide-Mimetic Methacrylate Random Copolymer Induces Domain Formation in a Model Bacterial Membrane.

To address the emerging issue of drug-resistant bacteria, membrane-active synthetic polymers have been designed and developed to mimic host-defense antimicrobial peptides (AMPs) as antibiotic alternatives. In this study, we investigated the domain formation induced by synthetic polymer mimics of AMPs using model membranes to elucidate the biophysical principles that govern their membrane-active mechanisms. To that end, lipid vesicles mimicking Escherichia coli (E. coli) membrane were prepared using an 8:2 (molar ratio) mixture of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1'-rac-glycerol), sodium salt (POPG). Our studies using differential scanning calorimetry (DSC) and fluorescence microscopy indicated that cationic amphiphilic methacrylate random copolymers induced the phase separation to form POPE- or POPG-rich domains. A rhodamine-labeled polymer also showed the binding to separated domains in the membrane. Based on these results, we propose the mechanism that the copolymers induce domain formation by clustering of anionic POPG lipids similar to natural AMPs. In addition, the time-course of polymer binding to the GUV membrane was sigmoidal, suggesting the positive feedback loop in the membrane binding. We also hypothesize that this cooperative binding of the polymer is driven by the domain formation. This study demonstrates the potential of the amphiphilic copolymers to modulate the lipid organization of cell membranes, which may provide a new strategy to design membrane-active antimicrobial agents.

Expression of thurincin H, ChiA74 and Cry proteins at the sporulation phase in Bacillus thuringiensis HD1.

AIMS: The objective of this study was to produce thurincin H, ChiA74 and Cry proteins together using Bacillus thuringiensis subsp. kurstaki HD1 as a heterologous host. METHODS AND RESULTS: pSTAB-ThurH and pSTAB-ChiA74 constructs were designed to produce thurincin H and chitinase, respectively, at the sporulation phase. They were transformed into Bt HD1 generating the recombinant strains HD1/pSTAB-ThurH and HD1/pSTAB-ThurH/pSTAB-ChiA74. Antimicrobial and chitinolytic activity tests were performed with recombinant strains. Both strains were able to produce thurincin H up to 72 h with antibacterial activity of ~4000 U mg-1 . The HD1/pSTAB-ThurH/pSTAB-ChiA74 strain also showed chitinolytic activity of ~23 mU mg-1 at 72 h. All B. thuringiensis strains exhibited crystal formation at 72, and 96 h. In addition, the application of thurincin H in corn seeds increased the germination percentage and root length by 7% and 10%, respectively. CONCLUSIONS: We showed that is possible to produce three proteins of biotechnological interest at the sporulation stage in B. thuringiensis, which two of them (thurincin H, and ChiA74) are naturally expressed in the vegetative stage. SIGNIFICANCE AND IMPACT OF THE STUDY: These results form the basis for developing of a biocontrol and biostimulator product that can be used as an alternative for chemical application.

Regulatory Mechanisms and Environmental Adaptation of the F-ATPase Family.

The F-type ATPase family of enzymes, including ATP synthases, are found ubiquitously in biological membranes. ATP synthesis from ADP and inorganic phosphate is driven by an electrochemical H+ gradient or H+ motive force, in which intramolecular rotation of F-type ATPase is generated with H+ transport across the membranes. Because this rotation is essential for energy coupling between catalysis and H+-transport, regulation of the rotation is important to adapt to environmental changes and maintain ATP concentration. Recently, a series of cryo-electron microscopy images provided detailed insights into the structure of the H+ pathway and the multiple subunit arrangement. However, the regulatory mechanism of the rotation has not been clarified. This review describes the inhibition mechanism of ATP hydrolysis in bacterial enzymes. In addition, properties of the F-type ATPase of Streptococcus mutans, which acts as a H+-pump in an acidic environment, are described. These findings may help in the development of novel antimicrobial agents.

Proton Pumping ATPases: Rotational Catalysis, Physiological Roles in Oral Pathogenic Bacteria, and Inhibitors.

Proton pumping ATPases, both F-type and V/A-type ATPases, generate ATP using electrochemical energy or pump protons/sodium ions by hydrolyzing ATP. The enzymatic reaction and proton transport are coupled through subunit rotation, and this unique rotational mechanism (rotational catalysis) has been intensively studied. Single-molecule and thermodynamic analyses have revealed the detailed rotational mechanism, including the catalytically inhibited state and the roles of subunit interactions. In mammals, F- and V-ATPases are involved in ATP synthesis and organelle acidification, respectively. Most bacteria, including anaerobes, have F- and/or A-ATPases in the inner membrane. However, these ATPases are not believed to be essential in anaerobic bacteria since anaerobes generate sufficient ATP without oxidative phosphorylation. Recent studies suggest that F- and A-ATPases perform indispensable functions beyond ATP synthesis in oral pathogenic anaerobes; F-ATPase is involved in acid tolerance in Streptococcus mutans, and A-ATPase mediates nutrient import in Porphyromonas gingivalis. Consistently, inhibitors of oral bacterial F- and A-ATPases, such as phytopolyphenols and bedaquiline, strongly diminish growth and survival. Herein, we discuss rotational catalysis of bacterial F- and A-ATPases, and discuss their physiological roles, focusing on oral bacteria. We also review the effects of ATPase inhibitors on the growth and survival of oral pathogenic bacteria. The features of the catalytic mechanism and unique physiological roles in oral bacteria highlight the potential for proton pumping ATPases to serve as targets for oral antimicrobial agents.

Surface-Textured Mixed-Metal-Oxide Nanocrystals as Efficient Catalysts for ROS Production and Biofilm Eradication.

Next-generation catalysts are urgently needed to tackle the global challenge of antimicrobial resistance. Existing antimicrobials cannot function in the complex and stressful chemical conditions found in biofilms, and as a result, they are unable to infiltrate, diffuse into, and eradicate the biofilm and its associated matrix. Here, we introduce mixed-FeCo-oxide-based surface-textured nanostructures (MTex) as highly efficient magneto-catalytic platforms. These systems can produce defensive ROS over a broad pH range and can effectively diffuse into the biofilm and kill the embedded bacteria. Because the nanostructures are magnetic, biofilm debris can be scraped out of the microchannels. The key antifouling efficacy of MTex originates from the unique surface topography that resembles that of a ploughed field. These are captured as stable textured intermediates during the oxidative annealing and solid-state conversion of ß-FeOOH nanocrystals. These nanoscale surfaces will advance progress toward developing a broad array of new enzyme-like properties at the nanobio interface.

Mycosynthesis of Metal-Containing Nanoparticles-Synthesis by Ascomycetes and Basidiomycetes and Their Application.

Fungi contain species with a plethora of ways of adapting to life in nature. Consequently, they produce large amounts of diverse biomolecules that can be generated on a large scale and in an affordable manner. This makes fungi an attractive alternative for many biotechnological processes. Ascomycetes and basidiomycetes are the most commonly used fungi for synthesis of metal-containing nanoparticles (NPs). The advantages of NPs created by fungi include the use of non-toxic fungus-produced biochemicals, energy efficiency, ambient temperature, pressure conditions, and the ability to control and tune the crystallinity, shape, and size of the NPs. Furthermore, the presence of biomolecules might serve a dual function as agents in NP formation and also capping that can tailor the (bio)activity of subsequent NPs. This review summarizes and reviews the synthesis of different metal, metal oxide, metal sulfide, and other metal-based NPs mediated by reactive media derived from various species. The phyla ascomycetes and basidiomycetes are presented separately. Moreover, the practical application of NP mycosynthesis, particularly in the fields of biomedicine, catalysis, biosensing, mosquito control, and precision agriculture as nanofertilizers and nanopesticides, has been studied so far. Finally, an outlook is provided, and future recommendations are proposed with an emphasis on the areas where mycosynthesized NPs have greater potential than NPs synthesized using physicochemical approaches. A deeper investigation of the mechanisms of NP formation in fungi-based media is needed, as is a focus on the transfer of NP mycosynthesis from the laboratory to large-scale production and application.

Pharmacotherapeutics Applications and Chemistry of Chalcone Derivatives.

Chalcones have been well examined in the extant literature and demonstrated antibacterial, antifungal, anti-inflammatory, and anticancer properties. A detailed evaluation of the purported health benefits of chalcone and its derivatives, including molecular mechanisms of pharmacological activities, can be further explored. Therefore, this review aimed to describe the main characteristics of chalcone and its derivatives, including their method synthesis and pharmacotherapeutics applications with molecular mechanisms. The presence of the reactive α,ß-unsaturated system in the chalcone's rings showed different potential pharmacological properties, including inhibitory activity on enzymes, anticancer, anti-inflammatory, antibacterial, antifungal, antimalarial, antiprotozoal, and anti-filarial activity. Changing the structure by adding substituent groups to the aromatic ring can increase potency, reduce toxicity, and broaden pharmacological action. This report also summarized the potential health benefits of chalcone derivatives, particularly antimicrobial activity. We found that several chalcone compounds can inhibit diverse targets of antibiotic-resistance development pathways; therefore, they overcome resistance, and bacteria become susceptible to antibacterial compounds. A few chalcone compounds were more active than conventional antibiotics, like vancomycin and tetracycline. On another note, a series of pyran-fused chalcones and trichalcones can block the NF-B signaling complement system implicated in inflammation, and several compounds demonstrated more potent lipoxygenase inhibition than NSAIDs, such as indomethacin. This report integrated discussion from the domains of medicinal chemistry, organic synthesis, and diverse pharmacological applications, particularly for the development of new anti-infective agents that could be a useful reference for pharmaceutical scientists.

Antimicrobial V-Shaped Copper(II) Pentaiodide: Insights to Bonding Pattern and Susceptibility.

Antimicrobial resistance (AMR) is a major concern for the survival of mankind. COVID-19 accelerated another silent pandemic of AMR through the uncontrolled use of antibiotics and biocides. New generations of antimicrobial agents are needed to combat resistant pathogens. Crown ethers can be used as models for drug action because they are similar to antibiotics. Iodine is a well-known microbicide but is characterized by instability and short-term effectivity. Iodine can be stabilized in the form of polyiodides that have a rich topology but are dependent on their immediate surroundings. In addition, copper has been successfully used since the beginning of history as a biocidal agent. We, therefore, combined iodine and copper with the highly selective crown ether 1,4,7,10-tetraoxacyclododecane (12-crown-4). The morphology and composition of the new pentaiodide [Cu(12-crown-4)2]I5 was investigated. Its antimicrobial activities against a selection of 10 pathogens were studied. It was found that C. albicans WDCM 00054 is highly susceptible to [Cu(12-crown-4)2]I5. Additionally, the compound has good to intermediate antimicrobial activity against Gram-positive and Gram-negative bacilli. The chain-like pentaiodide structure is V-shaped and consists of iodine molecules with very short covalent bonds connected to triiodides by halogen bonding. The single crystal structure is arranged across the lattice fringes in the form of ribbons or honeycombs. The susceptibility of microorganisms towards polyiodides depends on polyiodide bonding patterns with halogen-, covalent-, and non-covalent bonding.