Significant Bactericidal Activity Research Articles

Silver Linings: Electrochemical Characterization of TiO2 Sol-Gel Coating on Ti6Al4V with AgNO3 for Antibacterial Excellence

This study aimed to synthesize TiO2 and silver-containing TiO2 layers on Ti6Al4V titanium alloy substrates, also known as titanium grade 5 (TiGr5), to provide corrosion resistance and antibacterial activity. The TiO2 layers were prepared through the sol-gel method and dip-coating technique. Silver introduction into the layers was performed in two different ways. One was the impregnation method by dipping the TiO2 layer-covered metal in aqueous AgNO3 solutions of various concentrations (TiO2/AgNO3), and the other was by direct introduction of AgNO3 into the precursor sol (Ag-TiO2). The two methods for incorporating AgNO3 into the coating matrix are novel, as they preserve silver in its ionic form rather than reducing it to metallic silver. The samples were put through electrochemical characterization, namely potentiodynamic polarization and electrochemical impedance spectroscopy (EIS), and were tested in Hank’s solution, simulating a physiological environment. The behavior of the layers was monitored over time. Also, the thin layers’ thickness and adhesion to the substrate were determined. Microbiological evaluation of the Ag-doped coatings on glass substrates confirmed their significant bactericidal activity against Gram-negative Escherichia coli. Among the two types of coatings, the impregnated coatings demonstrated the most promising electrochemical performance, as evidenced by both EIS and potentiodynamic polarization analyses.

Synthesis, characterization and antibacterial activity of hexasubstituted Coumarin-based Schiff base derivative of cyclophosphazene

This study focuses on synthesis and characterization of hexa-substituted coumarin based Schiff base derivative of cyclotriphosphazene (Compound 3). The antibacterial activity of Compound 3 was evaluated against Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Pseudomonas aeruginosa (P. aeruginosa), and Klebsiella pneumoniae (K. pneumoniae) bacterial strains using minimum inhibitory concentration (MIC) and percentage-killing method. Compound 3 exhibited a lower MIC of 300 μg/mL against S. aureus than 500 μg/mL for P. aeruginosa and K. pneumoniae, indicating greater efficacy against Gram-positive bacteria. Percentage-killing data confirmed Compound 3 significant bactericidal activity against S. aureus across concentrations ranging from 100 to 500 μg/mL, comparable to ampicillin. In contrast, its efficacy against Gram-negative strains was lower, suggesting a more selective spectrum of activity. These findings suggest that Compound 3 shows promise as a potential antibacterial agent with preferential activity against Gram-positive bacteria, warranting further investigation into its mechanism of action and therapeutic potential.

Synthesis, biological evaluation, molecular docking analyses, and ADMET study of azo derivatives containing 1-naphthol against MβL-producing S. maltophilia

Stenotrophomonas maltophilia is a model organism exhibiting intrinsic antibiotic resistance, primarily due to its production of Mβ-lactamase enzymes that inactivate β-lactam antibiotics. This study aims to synthesize an azo derivative containing an oxazepine ring as a potential inhibitor of Mβ-lactamase. The molecular docking results revealed that the binding energies of the Mβ-lactamases ranged from − 5.95 to − 6.09 kcal/mol, indicating favourable interactions with the synthesized compounds. Two compounds were prepared: the first via aldol condensation of (A1) with p-hydroxybenzaldehyde to form (K1) and the second through Azo-Schiff base formation from 3,5-dimethylaniline, resulting in (L2) and (L18). Characterization of these compounds was conducted via FT-IR, CHN, 1H NMR, and 13C NMR spectroscopy. Antimicrobial activity was assessed through minimum inhibitory concentration (MIC) and minimum bacterial concentration (MBC) tests, which yielded values ranging from 1.19 ± 1 to 0.02 µg/mL and from 1.12 ± 1 to > 0.04 µg/mL, respectively. Notably, the MBC/MIC ratios indicated that L2 and L18 exhibited significant bactericidal activity. In silico analysis via MOE 2015 software allowed us to determine the binding poses and energies of the synthesized inhibitors against Mβ-lactamase (PDB ID: 6UAF). The most stable conformation from the docking results was selected for further evaluation. Compared with standard ceftazidime, the synthesized compounds significantly inhibited Mβ-lactamase activity. Additionally, ADMET analysis indicated favourable pharmacokinetic profiles and low toxicity, suggesting promising oral drug-like properties for the synthesized molecules.

Disrupting Mycobacterium smegmatis biofilm using enzyme-immobilized rifampicin loaded silk fibroin nanoparticles for dual anti-bacterial and anti-biofilm action

Biofilm formation is a major challenge in the treatment of tuberculosis, leading to poor treatment outcomes and latent infections. The complex and dense extracellular polymeric substances (EPS) of the biofilm provides safe harbour for bacterium enabling persistence against anti-TB antibiotics. In this study, we demonstrated that rifampicin-encapsulated silk fibroin nanoparticles immobilized with antibiofilm enzymes can disrupt the Mycobacterium smegmatis biofilm and facilitate the anti-bacterial action of Rifampicin (RIF). The EPS of M.smegmatis biofilm predominantly comprised of lipids (48.8 ± 1.32 %) and carbohydrates (34.8 ± 4.70 %), similar to tuberculosis biofilms. Pre-formed biofilm eradication screening revealed that hydrolytic enzymes such as β-Glucosidase, Glucose oxidase, ɑ-Amylase, Acylase, and Phytase can exhibit biofilm eradication of M.smegmatis biofilms. The enzyme-mediated biofilm disruption was associated with a decrease in hydrophobicity of biofilm surfaces. Treatment with β-glucosidase and Phytase demonstrated a putative biofilm eradication by reducing the total carbohydrates and lipid composition without causing any significant bactericidal activity. Further, Phytase (250 μg/ml) and β-Glucosidase (112.5 ± 17.6 μg/ml) conjugated rifampicin-loaded silk fibroin nanoparticles (R-SFNs) exhibited an enhanced anti-bacterial activity against pre-formed M.smegmatis biofilms, compared to free rifampicin (32.5±7 μg/ml). Notably, treatment with β-glucosidase, Phytase and ɑ-amylase immobilized SFNs decreased the biofilm thickness by ∼98.84 % at 6h, compared to control. Thus, the study highlights that coupling anti-mycobacterial drugs with biofilm-eradicating enzymes such as amylase, phytase or β-glucosidase can be a potential strategy to improve the TB therapeutic outcomes.

Therapeutic potential of green-synthesized silver nanoparticles: Combating biofilms of multidrug-resistant Staphylococcus aureus RM-Ph8 and modulating the immune response in the liver tissue of rats.

The emergence of multidrug-resistant Staphylococcus aureus (MRSA) strains poses a significant threat to healthcare settings. Although various studies have explored alternative antibiotics, discovering novel therapeutic agents remains crucial. This study aimed to synthesize green silver nanoparticles (AgNPs) as bactericidal agents, identify a multidrug-resistant isolate of Staphylococcus aureus, and explore their biofilm formation ability. To estimate the role of phyto-AgNPs in the perfection of immune markers and healing hepatic lesions in vivo. The clinical isolate of MRSA was identified using 16S rRNA New green AgNPs derived from Artemisia annua extract were synthesized. The nanoparticles (NPs) were characterized, and their minimum inhibitory concentration was estimated for fighting MRSA biofilm. A study was conducted on rats to evaluate the effect of new NPs on their immune response to MRSA infection. The new clinical isolate of MRSA RM-Ph8 was identified by molecular phylogenetic analysis as S. aureus, and 16S rRNA sequence analysis confirmed that the new strain was similar to S. aureus with 98.12% identity with accession number OQ421819. The FTIR of the new phyto-AgNPs displayed different functional groups that work as reducing silver nitrate agents. Transmission electron microscopy and scanning electron microscopy images showed spherical particles with an average diameter of 6-28 nm smaller. The chemical method led to complete cell destruction of the multidrug strain within 24 h. Biofilm formation showed that the new MRSA clinical strain was strongly adherent (88%). Notably, the phyto-AgNPs exhibited significant bactericidal activity against the new MRSA strain, with an MIC of up to 50 mg/mL. Moreover, phyto-AgNPs significantly decreased reversed MRSA-induced liver and kidney function impairment, with improvement in both the histopathological lesions and immune histochemical expression of tumor necrosis factor-α and inducible nitric oxide synthase at p < 0.05 compared with the untreated group. Green AgNPs are a promising therapeutic approach against multidrug-resistant bacterial infections, surpassing the effectiveness of conventional antibiotics.

Antibacterial and Antibiofilm potential of Thuja orientalis L. extract targeting cariogenic Enterococcus faecalis ATCC 29212: A combined in-vitro, in-silico study, and cytotoxicity screening

ObjectivesIn this study, we explored the efficacy of methanolic extract of Thuja orientalis (TOME) as a novel antibacterial and antibiofilm agent against a cariogenic bacterium, Enterococcus faecalis ATCC 29212. DesignAntibacterial susceptibility studies were conducted and surface morphology analysis was performed using field emission scanning electron microscopy (FESEM). Antibiofilm activity was evaluated through both qualitative and quantitative biofilm inhibition assays and validated by microscopic analysis. In-silico molecular docking studies were conducted using the EDock server. The effectiveness of TOME was substantiated by biofilm model on dentin discs and cytotoxicity towards the HaCaT cell line was assessed using the MTT assay. ResultsTOME exhibited significant bactericidal activity with minimum inhibitory concentration of 12.5mg/mL and additionally, it effectively compromised bacterial cell wall integrity. Qualitative, quantitative and microscopic studies depicted the inhibition of biofilm formation. TOME significantly impacted the production of extracellular polymeric substance and extracellular DNA. Molecular docking studies identified beta-caryophyllene as a potent inhibitor of the Enterococcal surface protein (Esp). Biofilm model depicted the reduction of bacterial load on dentin discs. Additionally, TOME showed reduced cytotoxicity on HaCaT cells, indicating its potential as a safe therapeutic agent. ConclusionThese findings highlight TOME's promise for developing novel treatments for dental infections and biofilm-associated diseases. Further research should focus on isolating and characterizing the active compounds within TOME, particularly beta-caryophyllene, to elucidate their precise mechanisms of action.

Linear electronic relationship of surface functionalized fly ash and substituted phenols on bactericidal activity with the computational study

AbstractFly ash is a solid waste by‐product obtained from coal‐burning power plants. It is a silico‐aluminate material with an admixture of several metal oxides, which finds an application in geopolymers, zeolites, cement, catalysts, etc. The present article aims to assess the antibacterial activity of fly ash and substituted phenols against Escherichia coli and Staphylococcus in broth and agar cultures, respectively. High‐Temperature Activated Fly Ash (TAFA) shows significant bactericidal activity against gram positive (+) and negative (−) bacteria as compared to Mechanically Activated Fly Ash (MAFA) and Waste Polyethylene Coated Fly Ash (WPCFA), which attribute to the augmentation of mullite phase (lacking charge balancing cation) of fly ash at high temperature. These modified fly ash (TAFA, MAFA, and WPCFA) were characterized by Fourier Transform Infra Red (FT‐IR), Scanning Electron Microscope (SEM), and X‐Ray Diffraction (XRD) techniques. The substituted phenols further explored the significance of charge on the antibacterial properties. The para‐substituted phenols with groups having (+) mesomeric effect M &gt; (−) I Inductive effect and ortho substituents with (+) I effect shows a linear electronic relationship with antibacterial properties with gram (+) bacteria, owing to charge augmentation at oxygen atom of phenoxide ion due to electronic effects. Further, the bactericidal efficacy was less significant on gram (−) bacteria. Small energy gap (Egap) values corroborated the chemical reactivity of phenols and substituted phenols. The antimicrobial potential of phenol/substituted phenols can be correlated with global descriptors. Molecular Electrostatic Potential (MEP) maps obtained through Density Functional Theory (DFT) indicate the nucleophilic centers in the molecular structure.

A novel antimicrobial peptide MP-4: Insights into its antimicrobial properties and intestinal regulation on E. coli-infected mice

The quest for novel, potent antimicrobial agents with low resistance potential poses a significant challenge for the advancement of the food and medical sectors. This study aimed to elucidate the antibacterial potency of antimicrobial peptides derived from koumiss in a murine model. Leveraging an antimicrobial peptide database, six peptides (MP-1 to MP-6) were meticulously predicted and screened for their antibacterial properties. These peptides were subsequently synthesized using chemical solid-phase methods and their antibacterial activities were rigorously validated. Remarkably, among the six peptides, MP-4 demonstrated a profound antibacterial effect against E. coli, achieving rapid bacterial eradication within 240 min. Flow cytometry analysis further corroborated its significant bactericidal activity. In vivo experiments conducted on mice infected with E. coli revealed that oral administration of MP-4 significantly ameliorated symptoms such as lethargy, anorexia, and weight loss. Additionally, it effectively reduced the colonic E. coli burden, attenuated inflammatory responses, and favorably modulated the intestinal microbiota composition. This study not only validates the robust antibacterial activity of the koumiss-derived antimicrobial peptide MP-4, but also underscores its potential therapeutic application in mitigating E. coli infections and promoting intestinal health.

In vitro Synergistic and Bactericidal Effects of Aztreonam in Combination with Ceftazidime/ Avibactam, Meropenem/Vaborbactam and Imipenem/Relebactam Against Dual-Carbapenemase-Producing Enterobacterales.

Our aim was to elucidate the resistance mechanisms and assess the combined synergistic and bactericidal activities of aztreonam in combination with ceftazidime/avibactam (CZA), meropenem/vaborbactam (MEV), and imipenem/relebactam (IMR) against Enterobacterales strains producing dual carbapenemases. Species identification, antimicrobial susceptibility testing and determination of carbapenemase type were performed for these strains. Plasmid sizes, plasmid conjugation abilities and the localization of carbapenemase genes were investigated. Whole-genome sequencing was performed for all strains and their molecular characteristics were analyzed. In vitro synergistic and bactericidal activities of the combination of aztreonam with CZA, MEV and IMR against these strains were determined using checkerboard assay and time-kill curve assay. A total of 12 Enterobacterales strains producing dual-carbapenemases were collected, including nine K. pneumoniae, two P. rettgeri, and one E. hormaechei. The most common dual-carbapenemase gene pattern observed was bla (KPC-2+NDM-5) (n=4), followed by bla KPC-2+IMP-26 (n=3), bla (KPC-2+NDM-1) (n=2), bla (KPC-2+IMP-4) (n=1), bla (NDM-1+IMP-4) (n=1) and bla (KPC-2+KPC-2) (n=1). In each strain, the carbapenemase genes were found to be located on two distinct plasmids which were capable of conjugating from the original strain to the receipt strain E. coli J53. The results of the checkerboard synergy analysis consistently revealed good synergistic effects of the combination of ATM with CZA, MEV and IMR. Except for one strain, all strains exhibited significant synergistic activity and bactericidal activity between 2 and 8 hours. Dual-carbapenemase-producing Enterobacterales posed a significant threat to clinical anti-infection treatment. However, the combination of ATM with innovative β-lactam/β-lactamase inhibitor compounds had proven to be an effective treatment option.

Mangosteen extract reduces the bacterial load of eggshell and improves egg quality

The increasing emergence and spread of antibiotic resistance accelerate the desire for antibiotic alternatives. Plant extracts have emerged as a promising and relatively unexplored area of research as potential substitutes. Herein, we investigated the prevalence and distribution patterns of bacteria on egg surfaces and evaluated the inhibitory effects of mangosteen extract on these surface bacteria. In addition, we examined the antioxidant activity and egg quality in improving the ability of mangosteen extract. The results showed that the predominant bacteria isolated from eggshells were Gram-positive, with Staphylococcus and Micrococcus as the dominant genera. Notably, mangosteen extract exhibited significant bactericidal activity, effectively inhibiting Gram-positive bacteria on the surface of chicken eggshells. Moreover, the supplementation of mangosteen extract in the feed of laying hens yielded a noteworthy improvement in egg quality, accompanied by positively shaped structure and function of microbial communities on the egg surface and in the feces. Collectively, our findings suggested that mangosteen extract was an effective alternative to traditional antibiotics, offering valuable insights for animal husbandry development.

A synthetic antibiotic class with a deeply-optimized design for overcoming bacterial resistance

The lack of new drugs that are effective against antibiotic-resistant bacteria has caused increasing concern in global public health. Based on this study, we report development of a modified antimicrobial drug through structure-based drug design (SBDD) and modular synthesis. The optimal modified compound, F8, was identified, which demonstrated in vitro and in vivo broad-spectrum antibacterial activity against drug-resistant bacteria and effectively mitigated the development of resistance. F8 exhibits significant bactericidal activity against bacteria resistant to antibiotics such as methicillin, polymyxin B, florfenicol (FLO), doxycycline, ampicillin and sulfamethoxazole. In a mouse model of drug-resistant bacteremia, F8 was found to increase survival and significantly reduce bacterial load in infected mice. Multi-omics analysis (transcriptomics, proteomics, and metabolomics) have indicated that ornithine carbamoyl transferase (arcB) is a antimicrobial target of F8. Further molecular docking, Isothermal Titration Calorimetry (ITC), and Differential Scanning Fluorimetry (DSF) studies verified arcB as a effective target for F8. Finally, mechanistic studies suggest that F8 competitively binds to arcB, disrupting the bacterial cell membrane and inducing a certain degree of oxidative damage. Here, we report F8 as a promising candidate drug for the development of antibiotic formulations to combat antibiotic-resistant bacteria-associated infections.

Influences of Bacillus pumilus SA388 as an environmentally friendly antibiotic alternative on growth performance, blood biochemistry, immunology, cecal microbiota, and meat quality in broiler chickens

The widespread use of antibiotics causes the development of antibiotic-resistant bacterial strains, which have a severe impact on poultry productivity and human health. As a result, research is continuing to develop safe natural antibiotic alternatives. In the current study, Bacillus pumilus SA388 was isolated from the chicken feces and confirmed to be a probiotic. The selected strain was tested for its antimutagenic and antioxidant capabilities before being employed as a probiotic food supplement and antibiotic alternative. The effect of B. pumilus SA388 impact on broiler chickens' growth performance, gut microbiome, blood biochemical markers, immunological response, and meat quality was also studied. B. pumilus SA388 showed significant bactericidal activity against Streptococcus pyogenes, Listeria monocytogenes, Staphylococcus aureus, Escherichia coli, Salmonella typhi, and Klebsiella pneumonia. A total of 200 chickens were used in the present study, divided equally among four experimental groups (ten birds per group with 5 replicates): group 1 (control, G1) received a basal diet without B. pumilus SA388, group 2 (G2) received a basal diet supplemented with 0.4 mg/kg of B. pumilus SA388, group 3 (G3) received a basal diet supplemented with 0.8 mg/kg of B. pumilus SA388, and group 4 (G4) received a basal diet supplemented with 1.6 mg/kg of B. pumilus SA388. Over 35 d, the B. pumilus SA388-supplemented groups outperformed the G1 in terms of body weight gain, performance index, and feed conversion ratio, with a preference for the G4 treatment. The levels of alanine aminotransferase (ALT), aspartate transaminase (AST), low-density lipoprotein (LDL), and total cholesterol decreased significantly (P < 0.05) with increasing B. pumilus SA388 dosages compared to the control G1 group. Dietary supplementation of B. pumilus SA388 at 1.6 mg/kg (G4) significantly (P < 0.05) resulted in improved lipid profile, immunological response, thyroid function, and gut microbiota compared to the control group (G1). Compared to the broilers in the control treatment (G1), the addition of B. pumilus SA388 to broilers in G4 significantly (P < 0.05) enhanced juiciness, tenderness, aroma, and taste. Adding B. pumilus SA388 to chicken feed at different doses significantly (P < 0.05) decreased average feed intake while increasing economic and relative efficiency measures. In conclusion, B. pumilus SA388 has been proven to be an effective antibiotic and nutritional supplement.

Efficacies of omadacycline + amikacin + imipenem and an all-oral regimen omadacycline + clofazimine + linezolid in a mouse model of M. abscessus lung disease.

Treatment outcomes for Mycobacteroides abscessus (Mab, also known as Mycobacterium abscessus) disease are still unsatisfactory, mainly due to issues with drug toxicity, tolerability, and efficacy. Treating Mab disease is challenging due to its high baseline antibiotic resistance, initial requirement for intravenous therapy, and poor medication tolerance. Omadacycline, a new tetracycline, is active against Mab. Since any new antibiotic effective against Mab is expected to be used in combination with other antibiotics, we evaluated the efficacy of two triple-drug combinations comprising omadacycline, omadacycline + amikacin + imipenem, and omadacycline + clofazimine + linezolid against two contemporary Mab clinical isolates in a mouse model of Mab lung disease. Antibiotic administration was initiated 1-week post-infection and was given daily, with Mab burden in the lungs at treatment completion serving as the endpoint. Omadacycline alone moderately reduced Mab levels and maintained better health in mice compared to untreated ones, which typically suffered from the infection. The omadacycline + clofazimine + linezolid combination showed immediate bactericidal activity and enhanced efficacy over 6 weeks, particularly against the more resistant strain (M9507). However, the clofazimine + linezolid combination lacked early bactericidal activity. When combined with amikacin and imipenem, omadacycline did not improve the regimen's effectiveness over 4 weeks of treatment. Our study showed that omadacycline + clofazimine + linezolid exhibited significant bactericidal activity over an extended treatment duration. However, adding omadacycline to amikacin and imipenem did not improve regimen effectiveness against the evaluated clinical isolates within 4 weeks. Further research in Mab disease patients is needed to determine the most effective omadacycline-containing regimen.IMPORTANCEMycobacteroides abscessus is a common environmental bacterium that causes infections in people with compromised lung function, including those with bronchiectasis, cystic fibrosis, chronic obstructive pulmonary disease, and weakened immune systems, especially among older individuals. Treating M. abscessus disease is challenging due to the limited effectiveness and toxicity of current antibiotics, which often require prolonged use. Omadacycline, a new antibiotic, shows promise against M. abscessus. Using a mouse model that mimics M. abscessus disease in humans, we studied the effectiveness of including omadacycline with recommended antibiotics. Adding omadacycline to clofazimine and linezolid significantly improved treatment outcomes, rapidly clearing the bacteria from the lungs and maintaining effectiveness throughout. This oral combination is convenient for patients. However, adding omadacycline to amikacin and imipenem did not improve treatment effectiveness within 4 weeks. Further study with M. abscessus patients is necessary to optimize omadacycline-based treatment strategies for this disease.

Thymoquinone as an electron transfer mediator to convert Type II photosensitizers to Type I photosensitizers

The development of Type I photosensitizers (PSs) is of great importance due to the inherent hypoxic intolerance of photodynamic therapy (PDT) in the hypoxic microenvironment. Compared to Type II PSs, Type I PSs are less reported due to the absence of a general molecular design strategy. Herein, we report that the combination of typical Type II PS and natural substrate carvacrol (CA) can significantly facilitate the Type I pathway to efficiently generate superoxide radical (O2–•). Detailed mechanism study suggests that CA is activated into thymoquinone (TQ) by local singlet oxygen generated from the PS upon light irradiation. With TQ as an efficient electron transfer mediator, it promotes the conversion of O2 to O2–• by PS via electron transfer-based Type I pathway. Notably, three classical Type II PSs are employed to demonstrate the universality of the proposed approach. The Type I PDT against S. aureus has been demonstrated under hypoxic conditions in vitro. Furthermore, this coupled photodynamic agent exhibits significant bactericidal activity with an antibacterial rate of 99.6% for the bacterial-infection female mice in the in vivo experiments. Here, we show a simple, effective, and universal method to endow traditional Type II PSs with hypoxic tolerance.

Synthesis of Bodipy-Tagged Galactoconjugates and Evaluation of Their Antibacterial Properties.

As a development of our research on biocompatible glycoconjugate probes and specifically multi-chromophoric systems, herein, we report the synthesis and early bactericidal tests of two luminescent glycoconjugates whose basic structure is characterized by two boron dipyrromethene difluoride (BODIPY) moieties and three galactoside rings mounted on an oligophenylene ethynylene (OPE) skeleton. BODIPY fluorophores have found widespread application in many branches of biology in the last few decades. In particular, molecular platforms showing two different BODIPY groups have unique photophysical behavior useful in fluorescence imaging. Construction of the complex architecture of the new probes is accomplished through a convergent route that exploits a series of copper-free Heck-Cassar-Sonogashira cross-couplings. The great emergency due to the proliferation of bacterial infections, in conjunction with growing antibiotic resistance, requires the production of new multifunctional drugs and efficient methods for their targeted delivery to control bacteria-associated diseases. Preliminary studies of the glycoconjugate properties as antibacterial agents against representatives of Gram-negative (P. aeruginosa) and Gram-positive (S. aureus) pathogens, which are associated with chronic infections, indicated significant bactericidal activity ascribable to their structural features.

In vitro and in vivo activity of ceftazidime/avibactam and aztreonam alone or in combination against mcr-9, serine- and metallo-β-lactamases-co-producing carbapenem-resistant Enterobacter cloacae complex.

Enterobacteriaceae carrying mcr-9, in particularly those also co-containing metallo-β-lactamase (MBL) and TEM type β-lactamase, present potential transmission risks and lack adequate clinical response methods, thereby posing a major threat to global public health. The aim of this study was to assess the antimicrobial efficacy of a combined ceftazidime/avibactam (CZA) and aztreonam (ATM) regimen against carbapenem-resistant Enterobacter cloacae complex (CRECC) co-producing mcr-9, MBL and TEM. The in vitro antibacterial activity of CZA plus ATM was evaluated using a time-kill curve assay. Furthermore, the in vivo interaction between CZA plus ATM was confirmed using a Galleria mellonella (G. mellonella) infection model. All eight clinical strains of CRECC, co-carrying mcr-9, MBL and TEM, exhibited high resistance to CZA and ATM. In vitro time-kill curve analysis demonstrated that the combination therapy of CZA + ATM exerted significant bactericidal activity against mcr-9, MBL and TEM-co-producing Enterobacter cloacae complex (ECC) isolates with a 100% synergy rate observed in our study. Furthermore, in vivo survival assay using Galleria mellonella larvae infected with CRECC strains co-harboring mcr-9, MBL and TEM revealed that the CZA + ATM combination significantly improved the survival rate compared to the drug-treatment alone and untreated control groups. To our knowledge, this study represents the first report on the in vitro and in vivo antibacterial activity of CZA plus ATM against CRECC isolates co-harboring mcr-9, MBL and TEM. Our findings suggest that the combination regimen of CZA + ATM provides a valuable reference for clinicians to address the increasingly complex antibiotic resistance situation observed in clinical microorganisms.

Experimental and molecular dynamics simulation study on antifouling performance of antimicrobial peptide‐modified aluminum alloy surfaces

Marine biofouling poses a major challenge to ship navigation and hinders the development of the shipping industry. Urgent action is required to tackle this problem through the implementation of innovative strategies. Antimicrobial peptides have garnered considerable attention due to their outstanding effectiveness, wide range of activity, and eco‐friendly characteristics. This study involved grafting the antibacterial peptide andricin 01 (AIGHCLGATL) onto the surface of an aluminum alloy, thereby creating a modified surface with antibacterial properties. In summary, amino groups were introduced onto the surface of aluminum alloys through the silanization process using (3‐aminopropyl) triethoxysilane (APTES), and then the peptides were covalently immobilized on the treated surface using glutaraldehyde as a cross‐linking agent. The successful modification of the peptide was confirmed by Fourier transform‐infrared spectroscopy (FT‐IR) and X‐ray photoelectron spectroscopy (XPS) analysis. The antimicrobial peptide‐modified aluminum alloy surfaces exhibited significant bactericidal activity, killing 75.3% of Bacillus sp. and 85.5% of Escherichia coli, while achieving antifouling efficiencies of 88.6% and 90.7% against Bacillus sp. and E. coli, respectively. Furthermore, molecular dynamics simulations showed that the inserted of the peptides into the phospholipid membrane caused a change in the local membrane curvature, which eventually led to membrane rupture. These results provide valuable information for the application of antimicrobial peptides in the field of antifouling and the elucidation of antifouling mechanisms.

Evaluation of the antimicrobial and antioxidant properties of synthetic phenolipids

Functionalization of phenolic compounds by lipophilization allowing the synthesis of new compounds with improved biological properties. This study aims to investigate the antimicrobial effects of eight synthesized phenolipids, derived from bioactive coumaric and ferulic acid esters, against Bacillus subtilis, Escherichia coli, and Candida albicans. Antioxidant activity, as well as antimicrobial capacity were evaluated through DPPH assays and classical disc agar diffusion, respectively, concomitantly with the evaluation of cellular viability using flow cytometry assay. Antioxidant activities results showed that ferulic acid esters exhibit higher antiradical activity than coumaric acid esters. Results of agar diffusion assay revealed that, 1-methylpropyl coumarate and 1-methylpropyl ferulate (1-MPF) have an effective antimicrobial activity with Minimum Inhibitory Concentrations (MICs) values between 0.9 and 3.5 mM against all tested microorganisms. Also, flow cytometry showed that 1-MPF and decyl coumarate exhibited significant bactericidal activity (p < 0.05), with almost 63 % of dead Bacillus subtilis cells. Compared to the commonly used agar method, flow cytometry proved to be a fast and straightforward analytical tool to assess antimicrobial activity while providing information on inhibition type. These results suggest the applicability of phenolipids as potent lipophilic bioactive molecules to protect food products and cosmetic formulations from oxidative stress and microbial spoilage.

Enhancing bactericidal activities of ciprofloxacin by targeting the trans-translation system that is involved in stress responses in Klebsiella pneumoniae.

Although the trans-translation system is a promising target for antcibiotic development, its antibacterial mechanism in Klebsiella pneumoniae (KP) is unclear. Considering that tmRNA was the core component of trans-translation, this study firstly investigated phenotypic changes caused by various environmental stresses in KP lacking trans-translation activities (tmRNA-deleted), and then aimed to evaluate antibacterial activities of the trans-translation-targeting antibiotic combination (tobramycin/ciprofloxacin) in clinical KP isolates based on inhibition activities of aminoglycosides against trans-translation. We found that the tmRNA-deleted strain P4325/ΔssrA was significantly more susceptible than the wild-type KP strain P4325 under environments with hypertonicity (0.5 and 1M NaCl), hydrogen peroxide (40mM), and UV irradiation. No significant differences in biofilm formation and survivals under human serum were observed between P4325/ΔssrA and P4325. tmRNA deletion caused twofold lower MIC values for aminoglycosides. As for the membrane permeability, tmRNA deletion increased ethidium bromide (EtBr) uptake of KP in the presence or absence of verapamil and carbonyl cyanide-m-chlorophenylhydrazone (CCCP), decreased EtBr uptake in presence of reserpine in P4325/ΔssrA, and reduced EtBr efflux in P4325/ΔssrA in the presence of CCCP. The time-kill curve and in vitro experiments revealed significant bactericidal activities of the tmRNA-targeting aminoglycoside-based antibiotic combination (tobramycin/ciprofloxacin). Thus, the corresponding tmRNA-targeting antibiotic combinations (aminoglycoside-based) might be effective and promising treatment options against multi-drug resistant KP.

Surface Modification of Zn-Cu Alloy with Heparin Nanoparticles for Urinary Implant Applications.

In this work, an investigation on the Zn-Cu alloy coated with heparin was conducted in order to explore the potentiality of its application as a feasible alternative for biodegradable implants, with the specific goal of addressing the issue of encrustation in the urinary system. The stability of the nanoparticles were characterized by dynamic light scattering. Typical surface characterization such as X-ray photoelectron spectroscopy, scanning electron microscopy, and atomic force microscopy were used to demonstrate a successful immobilization of the NPs. The in vitro corrosion behavior was studied by potentiodynamic polarization and immersion tests in artificial urine (AU) at 37 °C. The 8 weeks in vivo degradation, encrustation resistance, hemocompatibility, and histocompatibility were investigated by means of implantation into the bladders of rats. Both in vitro and in vivo degradation tests exhibited a higher degradation rate for Zn-Cu and NPs groups when compared to pure Zn. Histological evaluations and hemocompatibility revealed that there was no tissue damage or pathological alterations caused by the degradation process. Furthermore, antiencrustation performance and urinalysis results confirmed that the modified alloy demonstrated significant encrustation inhibitory properties and bactericidal activity compared to the pure Zn control. Our findings highlight the potential of this modified alloy as an antiencrustation biodegradable ureteral stent.