Active Antimicrobial Agents Research Articles

Light‐Activated Nanocatalyst for Precise In‐Situ Antimicrobial Synthesis via Photoredox‐Catalytic Click Reaction

AbstractThe excessive and prolonged use of antibiotics contributes to the emergence of drug‐resistant S. aureus strains and potential dysbacteriosis‐related diseases, necessitating the exploration of alternative therapeutic approaches. Herein, we present a light‐activated nanocatalyst for synthesizing in situ antimicrobials through photoredox‐catalytic click reaction, achieving precise, site‐directed elimination of S. aureus skin infections. Methylene blue (MB), a commercially available photosensitizer, was encapsulated within the CuII‐based metal–organic framework, MOF‐199, and further enveloped with Pluronic F‐127 to create the light‐responsive nanocatalyst MB@PMOF. Upon exposure to red light, MB participates in a photoredox‐catalytic cycle, driven by the 1,3,5‐benzenetricarboxylic carboxylate salts (BTC−) ligand presented in the structure of MOF‐199. This light‐activated MB then catalyzes the reduction of CuII to CuI through a single‐electron transfer (SET) process, efficiently initiating the click reaction to form active antimicrobial agents under physiological conditions. Both in vitro and in vivo results demonstrated the effectiveness of MB@PMOF‐catalyzed drug synthesis in inhibiting S. aureus, including their methicillin‐resistant strains, thereby accelerating skin healing in severe bacterial infections. This study introduces a novel design paradigm for controlled, on‐site drug synthesis, offering a promising alternative to realize precise treatment of bacterial infections without undesirable side effects.

Light-Activated Nanocatalyst for Precise In-Situ Antimicrobial Synthesis via Photoredox-Catalytic Click Reaction.

The excessive and prolonged use of antibiotics contributes to the emergence of drug-resistant S. aureus strains and potential dysbacteriosis-related diseases, necessitating the exploration of alternative therapeutic approaches. Herein, we present a light-activated nanocatalyst for synthesizing in situ antimicrobials through photoredox-catalytic click reaction, achieving precise, site-directed elimination of S. aureus skin infections. Methylene blue (MB), a commercially available photosensitizer, was encapsulated within the CuII-based metal-organic framework, MOF-199, and further enveloped with Pluronic F-127 to create the light-responsive nanocatalyst MB@PMOF. Upon exposure to red light, MB participates in a photoredox-catalytic cycle, driven by the 1,3,5-benzenetricarboxylic carboxylate salts (BTC-) ligand presented in the structure of MOF-199. This light-activated MB then catalyzes the reduction of CuII to CuI through a single-electron transfer (SET) process, efficiently initiating the click reaction to form active antimicrobial agents under physiological conditions. Both in vitro and in vivo results demonstrated the effectiveness of MB@PMOF-catalyzed drug synthesis in inhibiting S. aureus, including their methicillin-resistant strains, thereby accelerating skin healing in severe bacterial infections. This study introduces a novel design paradigm for controlled, on-site drug synthesis, offering a promising alternative to realize precise treatment of bacterial infections without undesirable side effects.

Description and Assessment of an Antimicrobial Substance from Marine Actinobacteria

Streptomyces is thought to be the primary source of bacteria for the synthesis of bioactive substances, such as naturally occurring antibiotics. Finding and identifying the actinomycetes exhibiting antagonistic activity was the primary goal of the current investigation. A strain of actinomycetes that was isolated from marine sand samples that were collected off the Indian coast of Vedharanyam exhibited antimicrobial activity against a number of microbial pathogens. The nutritional requirements and cultural conditions for maximal growth and yield of bioactive compounds have been optimized under shake flask condition. Analyze the compound characterization of the sample such as UV, FT-IR, GC-MS and sequencing 16S rRNA for species identification. The actinomycetes isolates which are isolated from sediment sample can be further used as antimicrobial activity agents against bacterial and fungal pathogens and their compound characterization.

In vitro Ascertainment of Interactions between Kanamycin and Adjuvants against Various Bacterial Species

Background: In recent times, there has been incontrovertible evidence regarding the propensity of various bacteria that barge through the immune system of an already debilitated individual. In this regard, combination therapy presents us with a more effective approach than conventional monotherapy. A specific combination of antibiotics exhibits a synergistic antibacterial effect, which can be seen with kanamycin, which shows moderate antibacterial activity alone but acts synergistically with particular adjuvants, displaying a high degree of antibacterial activity Objective: This study aimed to carry out an in vitro evaluation of the interaction between kanamycin and adjuvants against various bacterial species. Methods: The interaction between kanamycin and adjuvants against various bacterial isolates was determined by checkerboard assay, and the synergistic interactions were further evaluated by time-kill kinetic assay under in vitro settings. Results: The interaction between kanamycin and citric acid was found to be synergistic against all strains of E. coli. Both kanamycin and citric reduced their MICs by at least 4 fold in combination. This synergistic interaction was further confirmed by the time-kill kinetic assay. The result of time kill kinetic assay of combination revealed that at MIC, there was a 2.36 log10 CFU/ml reduction compared to kanamycin (the most active antimicrobial agent alone), at 24 hours at 2 fold MIC, 2.41 log10 CFU/ml reduction was seen in comparison to kanamycin at 24 hours at its one fold MIC. For other bacterial species, the combination of citric acid and kanamycin showed additive or indifferent interactions. In the case of our second combination (kanamycin and sodium salicylate), all the bacterial species displayed additive and indifferent interaction. Conclusion: It has been concluded that the combination of kanamycin and citric acid (adjuvant) demonstrated a remarkable synergistic interaction against E. coli.

Synthesis and Investigation of Biological Activity of New Betulonic Acid Derivatives Containing 1,2,3-Triazole Fragments.

The results of this study showed that the compounds synthesized by the authors have significant potential due to their antibacterial and cytotoxic properties. The apparent antibacterial activity demonstrated by the compounds suggests that they are active antimicrobial agents against common microbial pathogens that cause various socially significant infectious diseases. Compound 6 showed pronounced antimicrobial activity against the Gram-positive test strain Staphylococcus aureus ATCC 6538, and compound 7 demonstrated pronounced antimicrobial activity against the Gram-negative test strain Escherichia coli ATCC 25922 (MIC = 6.3 µg/mL). This allowed us to consider these compounds to have great potential.

Aspergillus Oryzae Mediated α‐Fe2O3 Nanoparticles for Photocatalytic Remediation of Basic Fuschin Dye and Antimicrobial Activities

AbstractGreen synthetic approach for the synthesis of Iron oxide (α‐Fe2O3) nanoparticles were successfully carried out using Aspergillus oryzae culture mediated biogenic route. The synthesized nanoparticle was confirmed by structural and optical characterization with the help of hematite phase. The α‐Fe2O3 nanoparticles show antimicrobial activity against bacterial strains Staphylococcus aureus, Pseudomonas aeruginosa and fungal strain Candida albicans. Under visible light, the α‐Fe2O3 nanoparticles demonstrate remarkable antibacterial action, confirming their superior efficacy for photocatalytic remediation. The present study discloses that the α‐Fe2O3 nanoparticles are efficient photocatalysts for 96 % degradation of basic fuchsin dye and highly active antimicrobial agent.

Ceramic Dressings-A New Non-Pharmacological Therapeutic Option in the Management of Chronic Wounds?

In this monocentric, intra-individually controlled, prospective study, patients with conservatively treated refractory chronic wounds were enrolled. One week before the start of the application with ceramic dressing, it was ensured during a screening phase that chronic wounds showed less than a 10% reduction in wound size. During the 4-week ceramic dressing treatment wound size measurements, wound scoring, measurement of wound exudate amount, wound swabs, and ceramic dressing sonication (low-intensity ultrasound) were carried out. The sonication fluid of the removed ceramic dressing was used for analysis of bacterial retention and compared to wound swabs. A total of 20 patients with a mean age of 64.6 years (±26.2) and 21 chronic wounds were included in this study. After a 4-week treatment, a significant reduction of median wound size from 1178 mm2 (range 104-6300) to 751.5 mm2 (range 16-4819) and better total wound scores were observed (p < 0.001). The sensitivity of bacteria detection was 90.7% in the sonication fluid from the ceramic dressings, while only 76.9% in the conventional wound swabs. The new ceramic dressing seems to have a positive impact on wound healing in chronic wounds. Bacteria-binding characteristics of the investigated ceramic dressing, in combination with its debridement, absorption, and detoxification properties, could contribute to its healing abilities. Based on those results, the investigated ceramic dressing seems to be a promising new treatment option for chronic wounds without the use of any active antimicrobial or pharmacological agents. Moreover, ceramic dressings can also be considered for microbiological diagnostic purposes.

The Synthesis and Antibacterial Activity of N-((1H-benzimidazol-2- yl)methyl)-2-substituted-3H- benzimidazol-5-amine Derivatives

Abstract: The increasing commonality of multi-drug-resistant bacteria as well as fungi is the motive for the development of new active antimicrobial agents. Heterocyclic compounds are major contributors in medical chemistry and are also found in biomolecules like vitamins, enzymes, natural products, etc. Benzimidazole is one of the nitrogens-containing heterocyclic compounds. Derivatives of benzimidazole have been found active against various bacterial diseases. Benzimidazole derivatives containing two benzimidazole rings also showed various pharmacological activities. In view of these, we aim to synthesize a new series of benzimidazole derivatives, N-((1H-benzimidazol-2-yl)methyl)-2-substituted-3H- benzimidazol-5-amine (6a–f) by the reaction of substituted 5-aminobenzimidazol derivatives with 2-chloromethyl benzimidazole and study their predicted bioactivity and actual antibacterial activity. To confirm the structures of the synthesized compounds, spectroscopic techniques like IR, 1H NMR,13C NMR and mass spectra were used. Initially, predicted bioactivity was studied using Molinspiration software. Among the synthesized compounds (6a-f), compounds 6a, 6d, 6e, and 6f showed good predicted activity. Then all the synthesized compounds 6a–f were screened for their antibacterial activity against E. coli (NCIM-2931), S. aureus (NCIM-2079), K. pnuemoniae (NCIM-2719) and P. aeruginosa (NCIM-2053) bacterial strains using the Ditchplate and Well Diffusion Method. Among them, compound 6f was found to be active against all used bacterial strains. Objectives: Synthesis and study of antimicrobial activity of benzimidazole derivatives. Methods: Simple, known laboratory methods are used for the synthesis of all new benzimidazole derivatives (6a-f). Predicted bioactivity was studied using Molinspiration software. The antibacterial activity of synthesized derivatives was studied against E. coli (NCIM-2931), S. aureus (NCIM-2079), K. pnuemoniae (NCIM-2719) and P. aeruginosa (NCIM-2053) bacterial strains using Ditch-plate and Well diffusion methods. Results: We successfully synthesized new bis-benzimidazole derivatives using simple laboratory methods and studied their antimicrobial activity. Among the synthesized derivatives, N-((1H-benzimidazol-2-yl)methyl)-2-(pyridin-3-yl)-3H-benzimidazol-5-amine (6f) showed good activity against used bacterial strains. Conclusion: In this paper, we report the synthesis of novel and biological activity benzimidazole derivatives by a simple and efficient method. The carried out predicted bioactivity as well as actual bioactivity was reported, and it was observed that predicted bioactivity and actual antibacterial activity showed similar results. The incorporation of a pyridine ring in a benzimidazole derivative increased bioactivity.

Dihydrophenazine: a multifunctional new weapon that kills multidrug-resistant Acinetobacter baumannii and restores carbapenem and oxidative stress susceptibilities.

The current work aims to fully characterize a new antimicrobial agent against Acinetobacter baumannii, which continues to represent a growing threat to healthcare settings worldwide. With minimal treatment options due to the extensive spread of resistance to almost all the available antimicrobials, the hunt for new antimicrobial agents is a high priority. An Egyptian soil-derived bacterium strain NHM-077B proved to be a promising source for a new antimicrobial agent. Bio-guided fractionation of the culture supernatants of NHM-077B followed by chemical structure elucidation identified the active antimicrobial agent as 1-hydroxy phenazine. Chemical synthesis yielded more derivatives, including dihydrophenazine (DHP), which proved to be the most potent against A. baumannii, yet it exhibited a marginally safe cytotoxicity profile against human skin fibroblasts. Proteomics analysis of the cells treated with DHP revealed multiple proteins with altered expression that could be correlated to the observed phenotypes and potential mechanism of the antimicrobial action of DHP. DHP is a multipronged agent that affects membrane integrity, increases susceptibility to oxidative stress, interferes with amino acids/protein synthesis, and modulates virulence-related proteins. Interestingly, DHP in subinhibitory concentrations re-sensitizes the highly virulent carbapenem-resistant A. baumannii strain AB5075 to carbapenems providing great hope in regaining some of the benefits of this important class of antibiotics. This work underscores the potential of DHP as a promising new agent with multifunctional roles as both a classical and nonconventional antimicrobial agent that is urgently needed.

Safety profile of ZnO active packaging PBAT based biomaterial for food packaging. First tier evaluation

Materials produced with polybutylene adipate terephthalate (PBAT) and starch are raising great interest for packaging and food contact applications, including as support for active antimicrobial agents such as zinc oxide nanoparticles (ZnO). Studies focusing on the safety of these materials as evaluated with the current reference rules for food contact materials, are lacking. A commercially available PBAT/starch-based material was incorporated with ZnO and the overall and specific migration of the films were studied at different conditions of simulants and temperature. The overall migration (OM) limit is exceeded due to the release of starch as confirmed by infrared spectroscopy. The impact of temperature on the OM was higher for the ethanol 10%. The incorporation of ZnO particles reduced the OM, for both temperatures tested for ethanol 10%. The impact of incorporating ZnO in the migration into acetic acid was relevant at 20 °C only. Beside starch, most relevant migrants were PBAT oligomers made of butanediol and two different kinds of diacids, terephthalic acid or adipic acid. The cyclic diester of 1,4-butanediol and adipic acid, butenyl butanediol adipate in either cyclic and linear form and oligomers terephthalic acid, but-3-enyl hexadecyl ester were detected in an untargeted screening with GC-MS. A second TPA oligomer was not fully identified. The specific migration was in several cases, depending on the simulant and on the temperature, higher than 50 μgkg−1 (semi-quantification), the threshold value for requiring additional toxicity test (genotoxicity tests applied to oligomers below 1000 Da). This indicates the need for more detailed studies with more precise quantification to verify the need for toxicity tests.

The antimicrobial activity of theobromine against cariogenic microbes: an in vitro pilot study

ObjectiveThis pilot study aimed to compare the antimicrobial effect of theobromine, sodium fluoride, and a theobromine-sodium fluoride combination against the following caries-associated bacteria: Streptococcus mutans and Actinomyces naeslundii.MethodologyAntimicrobial susceptibility was tested via the broth microdilution method, with suspensions cultured on each microbe’s respective selective media. Shapiro–Wilk’s was completed and all the data showed normality (p > 0.05), and One-way ANOVA was applied to infer the significant differences in the viable counts between the groups.ResultsAll experimental conditions for both S. mutans and A. naeslundii groups resulted in a significantly lower bacterial abundance in comparison to the control medium, without any active antimicrobial agent (p < 0.001). There was no significant difference in viable count between the theobromine, fluoride, or combination groups against either microbe (p > 0.05).ConclusionTheobromine’s antimicrobial activity against S. mutans and A. naeslundii was found similar to that of fluoride, whether used independently or in combination. Further testing of theobromine is necessary to assess its role as an alternative anticaries agent.

Investigation of anti‐inflammatory and antimicrobial activities of hydrazone‐based diorganotin (IV) complexes: Synthesis, spectroscopic characterization, and computational studies

In the search of novel and effective anti‐infectious agents, new hydrazone ligands (1–4) and their diorganotin (IV) complexes (5–20) were synthesized by condensing piperonylic hydrazide with salicylaldehyde derivatives, which have been further characterized by numerous physical and spectral techniques [1H, 13C, 119Sn] NMR, mass spectroscopy, UV–Vis, IR). These techniques ascertained dibasic tridentate coupling of hydrazone ligands with diorganotin (IV) through phenolic, enolic oxygens, and imine nitrogen, demonstrating pentacoordinated stereochemistry of the complexes. The thermal stability of up to 160°C of the complexes was ascertained by TGA studies whereas low conductance signified compounds have non‐electrolytic nature. Further, the antimicrobial activity was evaluated against four bacterial and two fungal strains by serial dilution assay, which demonstrated that the metal complexes (10, 11, 12) have comparable MIC values (0.0085–0.0098 μmol/ml) with ciprofloxacin and excellent biological responses in comparison of fluconazole. The phenyl complex [Ph2SnL2] (12) was found to be the most active antimicrobial agent with the lowest MIC value (0.0085 μmol/ml). The compounds were also screened for in vitro anti‐inflammatory activity by BSA denaturation assay and the phenyl complex [Ph2SnL2] (12) has been reported as most potent with 7.62 IC50 value, which is comparable with diclofenac sodium. Further, the biologically active complexes (9–12) and their hydrazone ligand [H2L2] were theoretically analyzed by computational investigations to support the in vitro results. The molecular docking analysis of compounds was performed on the active site of C. albicans (PDB ID: 5V5Z) and E. coli (PDB ID: 1HNJ) to assess the binding interactions and binding energy. The DFT and MESP (2, 9–12) revealed the most reactive areas, molecular geometry, Mulliken atomic charges, electronegativity, etc. of the compounds (2, 9–12). The ADMET profile showed the toxicity level and drug‐likeness properties, showing their potential to operate as viable antagonists.

Exploration of N‐(6‐Indazolyl) benzenesulfonamide Derivatives as Potential Antioxidants and Antimicrobial Agents: Integrating Synthesis, In Silico Docking, and Bioactivity Profiling

AbstractA new series of N‐(1‐(2‐chloropyrimidin‐4‐yl)‐1H‐indazol‐5‐yl) benzenesulfonamide derivatives (4 a–i) and N‐(1‐(2‐chloropyrimidin‐4‐yl)‐6‐ethoxy‐1H‐indazol‐5‐yl) benzenesulfonamide derivatives (5 a–i) was synthesized via reduction of 1‐(2‐halopyrimidin‐4‐yl)‐5‐nitro‐1H‐indazole (3) with SnCl2 followed by reaction with various aryl sulphonyl chlorides in pyridine. The structures were confirmed using IR, 1H‐NMR, 13C‐NMR, and mass spectral methods. Compounds 4 a–i and 5 a–i were evaluated for antifungal and antibacterial activities against Gram‐negative and Gram‐positive bacteria. They also exhibited antioxidant potential in DPPH (IC50=0.094‐0.467 μmol/ml) and ABTS assays (IC50=0.101–0.496 μmol/ml). Remarkably, N‐(1‐(2‐chloropyrimidin‐4‐yl)‐1H‐indazol‐5‐yl)‐2‐nitrobenzenesulfonamide displayed the highest antibacterial activity, while N‐(1‐(2‐chloropyrimidin‐4‐yl)‐1H‐indazol‐5‐yl)‐4‐methoxybenzenesulfonamide showed excellent antifungal potential. Compound N‐(1‐(2‐chloropyrimidin‐4‐yl)‐1H‐indazol‐5‐yl)‐2‐nitrobenzenesulfonamide exhibited the most significant antioxidant activity. In this study, molecular dynamics simulations were utilized to rigorously examine the stability of ligand‐protein complexes, demonstrating a consistent and robust binding of the most potent compound within the target proteins′ binding sites. Computational assessments were further employed to predict the drug‐likeness and ADMET properties of the synthesized compounds. The results unequivocally confirmed the remarkable antioxidant and antimicrobial potential of all derivatives, a finding substantiated by comprehensive molecular docking analyses that revealed intricate interactions involving hydrogen bonds, electrostatic forces, and hydrophobic contacts. These findings collectively provide invaluable insights into the complex molecular structure and receptor target site dynamics, laying a strong foundation for the development of novel active antioxidant and antimicrobial agents with promising pharmaceutical implications.

Quaternary Ammonium Salts of Cationic Lipopeptides with Lysine Residues — Synthesis, Antimicrobial, Hemolytic and Cytotoxic Activities

Ultrashort cationic lipopeptides (USCLs) and quaternary ammonium salts constitute two groups of cationic surfactants with high antimicrobial activity. This study aimed to investigate the influence of quaternization of the amino group of the lysine side chain in USCLs on their antimicrobial, hemolytic and cytotoxic activities. To do this, two series of lipopeptides were synthesized, USLCs and their quaternized analogues containing trimethylated lysine residues — qUSCLs (quaternized ultrashort cationic lipopeptides). Quaternization was performed on a resin during a standard solid-phase peptide synthesis with CH3I as the methylating agent. According to our knowledge, this is the first study presenting on-resin peptide quaternization. The lipopeptides were tested for their antibacterial and antifungal activities against the ESKAPE group (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella aerogenes) bacteria and Candida glabrata yeast-like fungus. Most of the compounds proved to be active antimicrobial agents with enhanced activity against Gram-positive strains and fungi and a lower against Gram-negative species. In addition, the antimicrobial activity of lipopeptides was increasing with an increase in hydrophobicity but qUSCLs exhibited usually a poorer antimicrobial activity than their parent molecules. Furthermore, the toxicity against red blood cells and human keratinocytes was assessed. It’s worth emphasizing that qUSCLs were less toxic than the parent molecules of comparative hydrophobicity. The results of the study proved that qUSCLs can offer a higher selectivity to pathogens over human cells than that of USCLs. Last but not least, quaternization of the peptides could increase their solubility and therefore their bioavailability and utility.

Synthesis, spectroscopic characterization, in vitro antimicrobial activity, antioxidant study and theoretical approaches towards DNA gyrase, DHFR enzyme, NADPH enzyme of N8-tetraoxomacrocyclic complexes of Zn(II)

In the present work, novel N8-tetraoxomacrocyclic complexes of Zn(II) were synthesized from macrocyclic ligands (N8O4L1- N8O4L3) in a 1:1 zinc chloride to macrocyclic ligand ratio in methanol solvent. The structure of the newly synthesized compounds was confirmed by elemental analysis, infra-red (IR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, high-resolution mass spectrometry (HR-MS), UV–visible spectroscopy, and powder X-ray diffraction (XRD) studies. The spectral data indicated that macrocyclic ligands (N8O4L1- N8O4L3) functioned as tetradentate ligands, which coordinated to Zn(II) ions through the nitrogen atom of imine (>CN) group. Two chloro groups are covalently bound to Zn(II) ions, which are responsible for an octahedral environment around the zinc in macrocyclic complexes. Density functional theory (DFT) calculations were performed to support the resulting proposed octahedral structure and also to calculate the quantum chemical parameters. Subsequently, the macrocyclic compounds were examined against a panel of pathogenic microbes including Gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis), Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa), and fungal strains (Aspergillus niger and Candida albicans) for their in vitro antimicrobial potential. The result showed that the macrocyclic complexes have remarkable antimicrobial potential as compared to their corresponding macrocyclic ligands at the same concentration. Then, the synthesized compounds were evaluated for their ability to scavenge free radicals using DPPH assay. The result showed that the macrocyclic complex [Zn(N8O4L3)Cl2] exhibited higher antioxidant efficacy among all the tested macrocyclic compounds with IC50 value 0.22 ± 0.025 mg/mL, relative to ascorbic acid (IC50 value = 0.12±0.01 mg/mL). Furthermore, molecular docking studies were performed to predict the exact binding mode of the newly synthesized compounds to the specified target proteins DNA gyrase (PDB ID 4DHU), DHFR enzymes (PDB ID 4HOF), and NADPH enzyme (PDB ID 2CDU). From the molecular docking studies, it was observed that the molecular docking results are in good agreement with the in vitro biological studies. Hence, it is concluded that macrocyclic ligands and their Zn(II) complexes have the potential to be explored as active antimicrobial and antioxidant agents.

Genomic analysis and antimicrobial activity of β-lactam/β-lactamase inhibitors and other agents against KPC-producing Klebsiella pneumoniae clinical isolates from Brazilian hospitals

Carbapenem-resistant Klebsiella pneumoniae (CRKP) are highly disseminated worldwide, and isolates co-resistant to other antimicrobial agents pose a threat to effective antimicrobial therapy. Therefore, evaluation of novel antimicrobial drugs is needed to identify potential treatments with better outcomes. We evaluated the in vitro activity of novel antimicrobial drugs/combinations against 97 KPC-producing Klebsiella pneumoniae isolates recovered from different hospitals in Brazil during 2021–2022. Clonality, resistance and virulence genes were detected by whole-genome sequencing. The majority of the isolates (54.6%) were classified as extensively drug resistant or multidrug resistant (44.3%); one isolate showed a pandrug resistance phenotype. The most active antimicrobial agents were meropenem-vaborbactam, cefiderocol, and ceftazidime-avibactam, with sensitivities higher than 90%; resistance to ceftazidime-avibactam was associated with KPC-33 or KPC-44 variants. Colistin and polymyxin B were active against 58.6% of the isolates. The 97 isolates were distributed into 17 different sequence types, with a predominance of ST11 (37.4%). Although high in vitro susceptibility rates were detected for meropenem-vaborbactam and cefiderocol, only ceftazidime-avibactam is currently available in Brazil. Our findings showed limited susceptibility to antimicrobial drugs employed for infection treatment of carbapenem-resistant K. pneumoniae, underscoring the urgent need for stringent policies for antimicrobial stewardship to preserve the activity of such drugs.

Design of phenothiazine-based cationic amphiphilic derivatives incorporating arginine residues: Potential membrane-active broad-spectrum antimicrobials combating pathogenic bacteria in vitro and in vivo

Multidrug-resistant bacteria infections pose an increasingly serious threat to human health, and the development of antimicrobials is far from meeting the clinical demand. It is urgent to discover and develop novel antibiotics to combat bacterial resistance. Currently, the development of membrane active antimicrobial agents is an attractive strategy to cope with antimicrobial resistance issues. In this study, the synthesis and biological evaluation of cationic amphiphilic phenothiazine-based derivatives were reported. Among them, the most promising compound 30 bearing a n-heptyl group and two arginine residues displayed potent bactericidal activity against both Gram-positive (MICs = 1.56 μg/mL) and Gram-negative bacteria (MICs = 3.125–6.25 μg/mL). Compound 30 showed low hemolysis activity (HC50 = 281.4 ± 1.6 μg/mL) and low cytotoxicity (CC50 ＞ 50 μg/mL) toward mammalian cells, as well as excellent salt resistance. Compound 30 rapidly killed bacteria by acting on the bacterial cell membrane and appeared less prone to resistance. Importantly, compound 30 showed potent in vivo efficacy in a murine model of bacterial keratitis. Hence, the results suggested compound 30 has a promising prospect as a broad-spectrum antibacterial agent for the treatment of drug-resistant bacterial infections.

Green nanocoating-based polysaccharides decorated with ZnONPs doped Egyptian kaolinite for antimicrobial coating paper

Paper coating plays an important role in the paper properties, printability and application. The nanocoating is a multifunction layer that provides the paper with unique features. In this work, nanocoating formulas were prepared using a green method and component. The nanocoating formulas were based on biopolymers nanostarch NSt and nanochitosan NCh (NCS) decorated with Egyptian kaolinite Ka doped with zinc nanoparticles NCS@xka/ZnONPs (x represents different ratios) support for multifunctional uses. The nanocoating formulas were characterized using a physiochemical analysis as well as a topographical study. FTIR, XRD, SEM and TEM techniques were used. Additionally, the antimicrobial activity of the tested samples was assessed against six microorganisms including Gram-negative and Gram-positive bacteria. The prepared nanocoating formulas affirmed excellent antimicrobial activity as a broad-spectrum antimicrobial active agent with excellent activity against all representative microbial communities. The nanocoating with the highest ratio of Ka/ZnONPs (NCS@40 ka/ZnONPs) showed excellent antimicrobial activity with an inhibition percentage of more than 70% versus all microorganisms presented. The paper was coated with the prepared suspensions and characterized concerning optical, mechanical and physical properties. When Ka/ZnONPs were loaded into NCS in a variety of ratios, the characteristics of coated paper were enhanced compared to blank paper. The sample NCS@40 ka/ZnONPs increased tensile strength by 11%, reduced light scattering by 12%, and improved brightness and whiteness by 1%. Paper coated with NCh suspension had 35.32% less roughness and 188.6% less porosity. When coated with the sample NCS@10 ka/ZnONPs, the coated paper's porosity was reduced by 94% and its roughness was reduced by 10.85%. The greatest reduction in water absorptivity was attained by coating with the same sample, with a reduction percentage of 132%.

Self-assembled and Zn(II)-coordinated dipeptide nanoparticles with membrane-rupturing action on bacteria.

Metal ion-coordinated self-assembled short-chain amino acid peptide molecules with multi-photon excitation wavelengths and their photoluminescence properties are advantageous for fluorescence-based diagnostics and treatments of biological diseases based on their extra features of antibacterial agents. We have designed a novel strategy based on tryptophan molecule coordinated with Zn(II) ions in the form of biocompatible spherical nanoparticles of diameter 30-80nm which have been used for antibacterial treatments against different kinds of pathogenic bacteria (Escherichia coli, Salmonella typhimurium, and Pseudomonas). Preferably, we have used tryptophan-phenylalanine (Trp-Phe), a dipeptide molecule having tryptophan as principal material against E. coli strains as antimicrobial agents for surface rupturing and killing purposes. Furthermore, based on single amino acid, tryptophan, self-assembled and Zn(II)-coordinated dipeptide nanoparticles (Zn-DPNPs) were studied against three types of multi-drug-resistant bacteria as an active antimicrobial agent. These antibacterial efficient nanoparticles may have best alternative of antibiotic drugs for clinical applications. The capability of self-assembled fluorescence behavior of Zn-coordinated dipeptide molecules and higher hydrophobicity against bacterial cell wall will perform as antimicrobial fluorescent agents. KEY POINTS: • Zn(II) and Cu(II) better coordinated into self-assembled NPs. • Fluorescence signals showed interaction of NPs with gram-ve cell wall. • Significant surface-damaging effects were observed in the case of Cu-DPNPs and Zn-DPNPs.

In Vitro Activity of Fosfomycin on Multidrug-Resistant Strains of Klebsiella pneumoniae and Klebsiella oxytoca Causing Urinary Tract Infection.

With the emergence of multi-drug resistant strains among Klebsiella isolates, the use of old drugs such as fosfomycin has been considered. In this context, we investigated the effect of fosfomycin on biofilm-producing Klebsiella pneumoniae and Klebsiella oxytoca strains isolated from ICU patients. A total of 90 isolates of Klebsiella pneumoniae and 30 isolates of Klebsiella oxytoca were collected from the ICU ward. All isolates were confirmed by biochemical and genotypic methods. Antibiotic susceptibility testing was performed by disc diffusion method and for fosfomycin and colistin, minimum inhibitory concentration (MIC) was done using micro broth dilution. The presence of the beta-lactamase encoding genes, biofilm-related genes, and fosfomycin resistance-related genes was detected by PCR. Finally, for fosfomycin-resistant isolates, we determined the sequence type by the MLST method. Sensitivity rate to fosfomycin in Klebsiella pneumoniae and Klebsiella oxytoca isolates was 92.2% and 100%, respectively. Fosfomycin was the most active antimicrobial agent with 96% sensitivity among all tested antibiotics. All tested isolates could produce biofilm. The frequency of biofilm-related genes for Klebsiella pneumoniae was as follows: 95.5% fimH, 86.6% mrkD, 77.7% mrkA, and 50% wcaG. The frequency of these genes for Klebsiella oxytoca was as follows: 56.6% fimA, 46.6% mrkA, 93.3% matB, and 90% pilQ. Only 4.4% of Klebsiella pneumoniae isolates showed resistance to fosfomycin, and the fosA gene was detected in all of them. Our results showed that fosfomycin effectively inhibits multidrug-resistant (MDR) strains of Klebsiella pneumoniae and Klebsiella oxytoca.