Minimum Inhibitory Concentration Research Articles

Phytochemical Study and In vitro Antibacterial Activities of Extracts from Three Ivorian Medicinal Plants Traditionally Used to Treat Inflammatory Dermatoses in the Mé Area, South-East of Ivory Coast

Background : Many of the pharmaceutical drugs used to treat Bacterial dermatoses, are becoming less and less effective in the face of bacterial multi-resistance. The search for remedies based on medicinal plants is a necessity in the discovery of new antibiotics effective in the treatment of dermatoses, above all inflammatory dermatoses become very common. Objective : To evaluate the antibacterial power of aqueous and ethanolics extracts of three medicinal plants used in traditional medicine by the Akyé people to treat inflammatory dermatoses. Methods : Plant organs were harvested in the Mé area, dried to a constant weight and then ground to a fine powder. Extraction was then carried out using osmosed water and ethanol 96° The phytochemical screening of the extracts was carried out by colouring reactions. The aqueous and ethanolic plant extracts were tested In vitro against Staphyloccocus aureus and Pseudomonas aeruginosa. Results : The phytochemistry screening revealed the presence of sterols and polyterpenes, polyphenols, alkaloids, flavonoids, tannins, quinones and saponosides. Antibacterial tests showed that the hydroethanol extracts were the most active, with Minimal Inhibitory Concentrations ranging from (0.048 to 06.25 mg/ml) and Minimal Bacterial Concentrations from (1.56 to 06.25 mg/ml). Of the two bacterial strains studied, Pseudomonas aeruginosa was the most sensitive to all the extracts. The antibacterial potentials thus highlighted by the values of the ratio between Minimal Bacterial Concentrations and Minimal Inhibitory Concentrations obtained indicated that all the extracts showed a high bactericidal activity (100%) on Pseudomonas aeruginosa compared with Staphylococus aureus. Conclusion : The results provide a solid database for future pharmaceutical research and the development of dermatological treatments derived from natural sources. In addition, this work highlights the importance of traditional medicinal knowledge in modern healthcare and supports efforts to develop effective topical forms of dermatoses based on active plant extracts through galenic formulations.

Metabolically Stable Adenylation Inhibitors of Biotin Protein Ligase as Antibacterial Agents.

The antibacterial agent Bio-AMS is metabolized in vivo through hydrolysis of the central acyl-sulfamide linker leading to high clearance and release of a moderately cytotoxic metabolite M1. Herein, we disclose analogues designed to prevent the metabolism of the central acyl-sulfamide moiety through steric hindrance or attenuation of the acyl-sulfamide electrophilicity. Bio-9 was identified as a metabolically stable analogue with a single-digit nanomolar dissociation constant for biotin protein ligase (BPL) and minimum inhibitory concentrations (MICs) against Mycobacterium tuberculosis and Staphylococcus aureus ranging from 0.2 to 20 μM. The antibacterial activity of Bio-9 was dependent on BPL expression level and was more than 70-fold better against a strain underexpressing BPL and, conversely, more than 5-fold less effective against a strain overexpressing BPL. Pharmacokinetic and metabolic studies demonstrated that Bio-9 was metabolically stable in vivo, showing negligible hydrolysis that translated to substantially reduced clearance and concomitantly boosted drug exposure and half-life compared to Bio-AMS.

In vitro evaluation of the immunomodulatory and antibacterial activities of calcitriol (1,25-dihydroxy-vitamin D3) as a potential application for aerobic vaginitis treatment - preliminary study results

BackgroundAerobic vaginitis (AV) is a state of abnormal vaginal microbiota, which is associated with increased numbers of aerobic, enteric bacteria and inflammation of the vaginal epithelium. Anti-microbial treatment combined with anti-inflammatory therapy could be useful in the treatment of this condition. It is known that calcitriol, the active form of vitamin D, plays an important role in modulating the immune response in several inflammatory diseases. The aim of this preliminary study was to evaluate in vitro the influence of calcitriol on the immune response of human vaginal epithelial cells to bacterial infection. Moreover, we assessed the anti-bacterial properties of calcitriol, as well as its synergistic activity with antibiotics that are used for the treatment of AV.ResultsHuman vaginal A431 epithelial cells were treated with calcitriol (100 nM) and then stimulated with thermally inactivated strains of AV-associated bacteria (Escherichia coli, Enterococcus faecalis, Streptococcus agalactiae), or first stimulated with heat-treated bacteria and then incubated with calcitriol (30 nM). After 24 h, 48 h, and 72 h post-infection, culture supernatants were collected, and levels of pro-inflammatory cytokines IL-6 and IL-1β were analyzed using enzyme-linked immunosorbent assays (ELISA). As it turned out, calcitriol treatment pre- or post-bacterial stimulation of vaginal epithelial cells significantly decreased the levels of IL-6 and IL-1β compared to cells stimulated only with bacteria. Downregulation of pro-inflammatory cytokines was more frequently significant when cells were pre-treated with calcitriol. Additionally, this study evaluated the anti-bacterial properties and synergistic activity of calcitriol with antibiotics by determining the Minimal Inhibitory Concentration (MIC) using colorimetric, Resazurin-based microdilution method detecting the active metabolism of bacteria. As a result, calcitriol by itself did not exhibit clinically relevant anti-bacterial activity; however, when combined with antibiotics, calcitriol significantly reduced the MIC values.ConclusionsThe results of this preliminary study confirm that calcitriol treatment influences cytokine-mediated immune response during infection and indicate that it can be effective in enhancing antibiotic activity. Such properties could be very useful in the treatment of inflammatory diseases. However, conclusions regarding the potential use of calcitriol in the treatment of AV require further confirmation in in vivo studies as well as in well-designed clinical trials.

Antimicrobial Susceptibility Profiles of Commensal Staphylococcus spp. Isolates from Chickens in Hungarian Poultry Farms Between 2022 and 2023

Background: Antimicrobial resistance is one of the greatest challenges of our time, urging researchers in both veterinary and public health to engage in collaborative efforts, thereby fostering the One Health approach. Infections caused by Staphylococcus species can not only lead to significant diseases in poultry but also pose serious threats to human life, particularly in hospital (nosocomial) infections; therefore, it is crucial to identify their antimicrobial resistance. Methods: Our objective was to assess the susceptibility profile of commensal Staphylococcus aureus strains (n = 227) found in commercial chicken flocks in Hungary through the determination of minimum inhibitory concentration (MIC) values. Results: Based on our findings, resistance to tiamulin (82.8%; 95% CI: 77.4–87.2%) and doxycycline (74.4%; 95% CI: 68.5–79.7%) is the most critical. The 55.1% (95% CI: 48.8–61.3%) resistance rate to enrofloxacin, a critically important antimicrobial, is also concerning. The fact that 58.6% (95% CI: 52.4–64.5%) of the strains were resistant to amoxicillin and 35.7% (95% CI: 29.7–42.1) were resistant to amoxicillin–clavulanic acid suggests that a proportion of the strains produce β-lactamase. Comparing our results with the available human hospital data, it was found that resistance to macrolide antibiotics is similarly high in both cases. Conclusions: Our findings highlight the necessity of conducting regular surveillance studies, which would allow the monitoring of future temporal trends. This information could benefit practitioners making clinical decisions to successfully treat infections. To uncover the underlying causes of multidrug resistance, next-generation sequencing can be employed to elucidate the genetic basis of phenotypic resistance.

Resorcinol-based Bolaamphiphilic Quaternary Ammonium Compounds.

Quaternary ammonium compounds (QACs) play crucial disinfectant roles in healthcare, industry, and domestic settings. Most commercially utilized QACs like benzalkonium chloride have a common architectural theme, leading to a rise in bacterial resistance and urgent need for novel structural classes. Some potent QACs such as chlorhexidine (CHX) and octenidine (OCT) feature a bolaamphiphilic architecture, comprised of two cationic centers at the molecular periphery and a non-polar region connecting them; these compounds show promise to elude bacterial resistance mechanisms. Inspired by such structures, we synthesized a series of 43 biscationic amphiphilic compounds focused on a resorcinol core, featuring flexibility of linker lengths, alkyl tails, and relative substituent positioning, to study their structure activity relationships (SARs). Antibacterial activity evaluation against a panel of gram-positive and gram-negative strains, including ESKAPE pathogens (A. baumannii,P. aeruginosa), were encouraging, with minimum inhibitory concentrations (MICs) of 0.5-4 μM against all tested strains for select compounds. Ten prepared compounds bearing either 17 or 18 total side chain carbons demonstrated uniformly strong antibacterial activity againstP. aeruginosa(MIC 4-16 μM) and 6 other strains (MIC ≤4 μM), irrespective of cationic spacing.These findings promise to further extend the application of bolaamphiphilic QACs as a novel class of disinfectants.

In Vitro Determination of Antimicrobial, Antioxidant and Antiviral Properties of Greek Plant Extracts

The medicinal potential of plant extracts, especially their antimicrobial, antioxidant, antiviral and cytotoxic properties, has gained significant attention in recent years. This study examined the in vitro bioactivities of several selected Greek medicinal plants, like Eucalyptus globulus L., Thymus vulgaris L., Salvia rosmarinus L. and Ocimum basilicum L., are well-known for their traditional therapeutic use. Minimum inhibitory concentration (MIC) assays were used to evaluate the antimicrobial activity of the extracts against pathogenic bacteria. The antioxidant activity was carried out using the DPPH method, while the cytotoxicity of the plants was determined using the Alamar Blue method. In addition, the antiviral efficacy of the samples was tested against DENV in different cell lines. The majority of medicinal herbs demonstrated significant antimicrobial action (MIC = 30–3000 μg∙mL−1). The extracts showed great antioxidant activity, while the Salvia rosmarinus L. extract turned out to be the most effective (IC50 = 12.89 ± 0.11 μg∙mL−1). In contrast, the extract of Eucalyptus globulus L. had the lowest antioxidant action (IC50 = 71.02 ± 0.42 μg∙mL−1). The results of the Alamar Blue method were presented with CC50 values, and it was shown that Eucalyptus globulus L. extract exhibited the highest cytotoxicity (CC50 = 5.94% v/v ± 0.04). Similarly, the results of the antiviral potential of extracts were expressed as EC50 values, and Eucalyptus globulus L. was characterized as the most effective sample against dengue virus infection, with EC50 values estimated at 2.37% v/v ± 0.6 (HuhD-2 cells infected with DENV-2) and 0.36% v/v ± 0.004 (Huh7.5 cells infected with DVR2A). These findings provide a foundation for further studies in order to combat infectious diseases and promote human health.

Phytochemical Screening, Antioxidant Test and Antimicrobial Test of Streptococcus Mutans and Candida Albicans from Extracts of Ultrasound Assisted Extraction of Red Betel Leaves (Piper Ornatum N. E. Br)

Red betel (Piper ornatum) is an ornamental plant with potential antibacterial and antioxidant properties due to its bioactive compounds, including alkaloids, flavonoids, steroids, triterpenoids, saponins, and tannins. This study aimed to determine the relationship between flavonoid content, antioxidant activity, and antimicrobial activity in red betel leaves. Ultrasound-Assisted Extraction (UAE) was employed using three solvents of varying polarity: n-hexane (non-polar), ethyl acetate (semi-polar), and ethanol (polar). Total flavonoid content was determined spectrophotometrically based on flavonoids' ability to form complexes with AlCl3. Antioxidant activity was assessed using the DPPH (2,2-diphenyl-1-picrylhydrazyl) method. Antibacterial and antifungal properties were evaluated through Minimum Inhibitory Concentration (MIC) and Zone of Inhibition (ZOI) tests. MIC was determined using the agar dilution method, while ZOI was measured using the disc diffusion method. Results showed that the 96% ethanol extract yielded the highest flavonoid content (4.748%) and the strongest antioxidant activity (IC50 = 47.185 ppm, classified as very strong). The n-hexane extract at 25% concentration exhibited the best antibacterial activity against Streptococcus mutans (ZOI = 17.43 mm), while the 96% ethanol extract at 25% concentration demonstrated the highest antifungal activity against Candida albicans (ZOI = 17.02 mm). In conclusion, red betel leaf extracts show promising potential as strong antioxidants and antimicrobial agents against C. albicans and S. mutans.

3D QASR, Antimicrobial Activity and Molecular Docking Studies of C-14 Chiral Matrine Derivatives as Potential Antibiotics.

Antibiotic resistance is recognized as one of the top ten global public health threats, posing a significant challenge to human health. The stereochemistry of chiral molecules, alongside their specific interactions with biological targets, provides essential insights for the development of novel antibacterial agents, This study investigated the antibacterial activity of 32 previously synthesized 14-position chiral matrine derivatives. Among these derivatives, compound Q4 exhibited the strongest activity against Propionibacterium acnes, with a minimum inhibitory concentration (MIC) of 0.007 mg/mL, surpassing that of the positive control (MIC = 0.016 mg/mL). Additionally, compounds Q20 and Q2 demonstrated antibacterial activities comparable to the positive controls. The results indicated that R-configured compounds exhibited significantly greater antibacterial potency than their S-configured counterparts. A systematic analysis using 3D-QSAR modeling elucidated the relationship between molecular structure and antibacterial activity, emphasizing the predominance of steric fields over electrostatic fields, in alignment with experimental observations. Furthermore, molecular docking confirmed the binding interactions between compound Q4 and the target protein. In conclusion, C-14 chiral matrine derivatives exhibit considerable potential as effective antibacterial agents, meriting further exploration in the search for new treatments to combat antibiotic-resistant infections.

Dissemination of IncQ1 Plasmids Harboring NTEKPC-IId in a Brazilian Hospital

KPC is a clinically significant serine carbapenemase in most countries, and its rapid spread threatens global public health. blaKPC transmission is commonly mediated by Tn4401 transposons. The blaKPC gene has also been found in non-Tn4401 elements (NTEKPC). To fill the gap in the understanding of the stability and dissemination of NTEKPC-carrying plasmids, we selected and characterized carbapenem-resistant bacteria isolated between 2009 and 2016 from a hospital for a retrospective study of their plasmids conjugation capacity, impact on fitness, and replication in different species. Different clones were selected using PFGE, and their genomes were sequenced using Illumina and Oxford Nanopore methods. Minimum inhibitory concentrations (MICs) were determined by broth microdilution. Plasmid copy numbers (PCNs) were determined using qPCR. Doubling time was used to analyze fitness change. Most isolates (67%, 33/49) carried blaKPC, of which 85% presented blaKPC in a NTEKPC. The 25 isolates selected presented the blaKPC gene in NTEKPC-IId in IncQ1-type plasmids, showing multispecies dissemination. IncQ1 plasmids were mobilizable and PCN seemed to be directly linked to the species, presenting a high-copy number, mainly in K. pneumoniae. No relationship was observed between IncQ1 PCN and carbapenems MIC values. IncQ1 and a conjugative plasmid from K. pneumoniae BHKPC10 were transferred to E. coli J53 without fitness changes, and MIC values were maintained for carbapenems despite the low transconjugant PCN. In addition to IncQ1 with NTEKPC, Enterobacter cloacae BHKPC28 contained the mcr-9 gene in an IncHI2/IncHI2A conjugative plasmid, which may help the mobility of IncQ1 and the dissemination of two resistance determinants to last-resort antibiotics. Understanding the interaction between plasmids and high-risk lineages can help develop new therapies to prevent the dissemination of resistance traits.

Dosage Optimization Using Physiologically Based Pharmacokinetic Modeling for Pediatric Patients with Renal Impairment: A Case Study of Meropenem.

The pharmacokinetics of renally eliminated antibiotics can be influenced by changes associated with renal function and development in a growing subject. Little is known about the effects of renal insufficiency on the pharmacokinetics of meropenem in pediatric subjects. The aim of this study was to develop a physiologically based pharmacokinetic (PBPK) model of meropenem for pediatric patients that can be used to optimize meropenem dosing in pediatric patients with renal impairment (RI). The PBPK model was developed using GastroPlus™ 9.9 based on clinical data obtained from the literature and then scaled to pediatric patients with RI for dose optimization of meropenem. The goodness of fit of the model was assessed by comparing the predicted values of AUC0-t, AUC0-α, and Cmax with the observed data and the average fold errors (AFE). The AFE values for AUC0-t, AUC0-α, and Cmax in the pediatric population were measured to be 1.60, 1.08, and 1.48, respectively. In addition, dose optimization was performed in virtual pediatric populations with varying degrees of RI and a dose reduction to 10mg/kg and 7.5mg/kg was recommended for moderate and severe RI, respectively. In all virtual pediatric populations with RI, the plasma concentration reached the recommended time above the minimum inhibitory concentration (MIC) at all optimized doses. The developed PBPK model for meropenem provides a quantitative tool to assess the impact of RI on the pharmacokinetics of meropenem in pediatric patients, which may be useful for optimizing the dosing regimen.

Pharmacodynamic Profiling of Amoxicillin: Targeting Multidrug-Resistant Gram-Positive Pathogens Staphylococcus aureus and Staphylococcus pseudintermedius in Canine Clinical Isolates

The rising threat of antimicrobial resistance (AMR) is a global concern in both human and veterinary medicine, with multidrug-resistant (MDR) pathogens such as Staphylococcus aureus and Staphylococcus pseudintermedius presenting significant challenges. Background/Objectives: This study evaluates the effectiveness of amoxicillin against these MDR pathogens in canine isolates using pharmacokinetic and pharmacodynamic parameters. Methods: Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and mutation prevention concentration (MPC) were assessed. Additionally, time-kill assays and post-antibiotic effect (PAE) assessments were performed. Epidemiological cutoff (ECOFF) values were established for both species to guide therapy. Results: S. aureus had a higher resistance rate (35.89%) than S. pseudintermedius (15.27%), with MIC50 values of 0.50 μg/mL and 0.25 μg/mL, respectively. The MPC analysis revealed that S. pseudintermedius required higher antibiotic concentrations (16.11 μg/mL) to prevent mutations compared to S. aureus (2.20 μg/mL). Time-kill assays indicated that higher amoxicillin dosages caused faster bacterial reduction. The PAE analysis showed extended post-treatment bacterial suppression at elevated doses, particularly against S. aureus. Conclusions: Species-specific amoxicillin dosing strategies are necessary due to differing resistance and susceptibility profiles between S. aureus and S. pseudintermedius. High-dose amoxicillin therapy is recommended to achieve optimal therapeutic outcomes for resistant SA, while slightly adjusted dosing can manage S. pseudintermedius infections. These findings provide essential insights for veterinary antimicrobial stewardship, underscoring the need for tailored therapeutic approaches to minimize AMR development while ensuring effective infection control.

Exploring Antibacterial Properties of Marine Sponge-Derived Natural Compounds: A Systematic Review

The rise in multidrug-resistant (MDR) bacteria has prompted extensive research into antibacterial compounds, as these resistant strains compromise current treatments. This resistance leads to prolonged hospitalization, increased mortality rates, and higher healthcare costs. To address this challenge, the pharmaceutical industry is increasingly exploring natural products, particularly those of marine origin, as promising candidates for antimicrobial drugs. Marine sponges, in particular, are of interest because of their production of secondary metabolites (SM), which serve as chemical defenses against predators and pathogens. These metabolites exhibit a wide range of therapeutic properties, including antibacterial activity. This systematic review examines recent advancements in identifying new sponge-derived compounds with antimicrobial activity, specifically targeting Pseudomonas aeruginosa, a prevalent Gram-negative pathogen with the highest incidence rates in clinical settings. The selection criteria focused on antimicrobial compounds with reported Minimum Inhibitory Concentration (MIC) values. The identified SM include alkaloids, sesterterpenoids, nitrogenous diterpene, and bromotyrosine-derived derivatives. The structural features of the active compounds selected in this review may provide a foundational framework for developing new, highly bioactive antimicrobial agents.

Evaluating the antibacterial efficacy of bee venom against multidrug-resistant pathogenic bacteria: Escherichia coli, Salmonella typhimurium, and Enterococcus faecalis

Bee venom (BV) represents a promising natural alternative to conventional antibiotics, particularly significant given its broad-spectrum antimicrobial activity and potential to address the growing challenge of antimicrobial resistance. The prevalence of antimicrobial-resistant microorganisms (AMR) is a global burden that affects human health and the economies of different countries. As a result, several scientific communities around the world are searching for safe alternatives to antibiotics. In this context, the present study represents a comprehensive investigation to evaluate the antibacterial effect of bee venom (BV) against Escherichia coli ATCC8739, Salmonella typhimurium ATCC14028, and Enterococcus faecalis ATCC25923. One mg of BV was extracted using 1 mL of DMSO to obtain a 1000 µg/mL solution. The chemical profile of the BV extract was determined using GC-MS, which revealed the presence of bioactive molecules with antimicrobial properties, such as astaxanthin, hycanthone, and fucoxanthin. The BV extract was tested against bacterial strains using different concentrations to obtain the minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC). The results obtained revealed a high antibacterial activity of BV against the three strains with the highest MIC/MBC values of 12.5/25 µgml− 1 against S. typhimurium. The antibacterial activity of the BV extract was compared to five conventional antibiotics using the disc diffusion method. The results showed a high antibacterial activity of the BV extract compared to different antibiotics with the largest inhibition zone obtained against E. faecalis at a value of 15 ± 0.22 mm compared to 9 ± 0.13 for azithromycin. The mode of action of BV, examined using scanning electron microscopy, proved a high effect of BV on the permeability of the bacterial plasma membrane. This study demonstrates bee venom’s promising potential as a natural and eco-friendly antimicrobial agent, with activity against multiple bacterial strains, suggesting it may serve as an alternative to conventional antibiotics. The findings highlight the potential applications of BV in medical, agricultural, and veterinary fields, offering a sustainable solution to combat antimicrobial resistance. However, further studies are needed to fully assess its broad-spectrum antibacterial potential.Clinical trial number Not applicable.

Genome-Guided Identification and Characterisation of Broad-Spectrum Antimicrobial Compounds of Bacillus velezensis Strain PD9 Isolated from Stingless Bee Propolis.

The emergence of multidrug-resistant pathogens presents a significant global health challenge, which is primarily fuelled by overuse and misuse of antibiotics. Bacteria-derived antimicrobial metabolites offer a promising alternative strategy for combating antimicrobial resistance issues. Bacillus velezensis PD9 (BvPD9), isolated from stingless bee propolis, has been reported to have antibacterial activities against methicillin-resistant Staphylococcus aureus (MRSA). This study aimed to characterise and identify the antimicrobial compounds (AMCs) synthesised by BvPD9 through integration of genome mining and liquid chromatography-mass spectrometry (LC-MS) analysis. The whole-genome sequence of BvPD9 contained 4,263,351 base pairs and 4101 protein-coding sequences, with 12 potential AMC biosynthetic gene clusters. Comparative genomic analysis highlighted the unique profile of BvPD9 that possesses the largest number of unknown proteins, indicating significant potential for further exploration. The combined genomics-metabolic profiling uncovered five AMCs in BvPD9 extract, including bacillibactin, bacilysin, surfactin A, fengycin A, and bacillomycin D. The extract exhibited a broad antibacterial spectrum against 25 pathogenic bacteria, including both Gram-positive and Gram-negative bacteria, with the lowest minimum inhibitory concentration (MIC, 0.032mg/ml) against S. epidermidis ATCC 12228, and the lowest minimum bactericidal concentration (MBC; 0.128mg/ml) against MRSA ATCC 700699 and Aeromonas hydrophilia. The robust stability of BvPD9 extract was demonstrated at high temperatures, over a wide range of pH conditions (6 to 12) and in the presence of various hydrolytic enzymes. Additionally, the extract showed 50% haemolytic and cytotoxicity activity at 0.158 and 0.250mg/ml, respectively. These characteristics suggest potential applications of BvPD9 metabolites for tackling antimicrobial resistance and its applicability across diverse industries.

Biosynthesis and activity of Zn-MnO nanocomposite in vitro with molecular docking studies against multidrug resistance bacteria and inflammatory activators

This study investigated the green synthesis of Zn-MnO nanocomposites via the fungus Penicillium rubens. Herein, the synthesized Zn-MnO nanocomposites were confirmed by UV-spectrophotometry with a top peak (370 nm). Transmission electron microscopy confirmed irregular particles with a spherical-like shape ranging from 25.13 to 36.21 nm. Numerous functional groups were detected on the surface of Zn-MnO nanocomposite via Fourier-transform infrared spectroscopy. X-Ray diffraction assay appeared that the synthesized Zn-MnO nanocomposites contained two different components, MnO (JCPDS 81-2261) and ZnO (JCPDS 36-1451), while energy dispersive X-ray spectra confirmed the occurrence of manganese, zinc, oxygen, and carbon in Zn-MnO nanocomposites. Zn-MnO nanocomposites demonstrated excellent suppress effect versus the growth of various bacteria namely Staphylococcus aureus, Methicillin-resistant S. aureus (MRSA), Salmonella typhi, and Klebsiella pneumoniae via agar well diffusion assays with inhibition areas of 36 ± 0.1, 25 ± 0.1, 27 ± 0.2, and 23 ± 0.2 mm, correspondingly. Alterations in the ultrastructure of the treated K. pneumoniae by Zn-MnO nanocomposite were recorded. Both the values of minimum inhibitory concentration (MIC) and minimum bactericidal concentration of Zn-MnO nanocomposite extended from 15.62 to 125 µg/mL employing the examined bacteria. The antibiofilm activity of Zn-MnO nanocomposites was 82.07, 75.43, 43.65, and 41.35% at 25% MIC, and 96.54, 93.0, 94.53, and 91.11% at 75% MIC against S. aureus, MRSA, K. pneumoniae, and S. typhi, respectively. At 25 to 75% MIC, Zn-MnO nanocomposites exhibited antihemolytic activity with the maximum activity of 96.3% at 75% MIC in the presence of MRSA. Extensive molecular docking studies were performed to identify the optimal location for manganese oxide and zinc oxide nanoclusters binding to MRSA. MnO-NPs and ZnO-NPs demonstrated inhibitory activity against the crystal structure of putative minohydrolase (PDB ID: 4EWT), methicillin acyl-penicillin binding protein 2a structure (PDB ID: 1MWU) and K2U bound crystal structure of class II peptide deformylase from MRSA (PDB ID: 6JFQ). The minimum binding energy was utilized to estimate the receptor’s binding site with NPs, providing additional understanding of the ways of action. Anti-inflammatory activity of Zn-MnO nanocomposites via cyclooxygenase-1 and cyclooxygenase-2 enzymes inhibition was documented with IC50 doses of 20.81 ± 0.68 µg/mL and 35.87 ± 1.35 µg/mL, respectively. Based on these outcomes, it was concluded that Zn-MnO nanocomposites could be useful agents for the management of multidrug resistant bacterial pathogens and inflammation.

Betaine combined with traditional Chinese medicine ointment to treat skin wounds in microbially infected diabetic mice.

Skin wounds are highly common in diabetic patients, and with increasing types of pathogenic bacteria and antibiotic resistance, wounds and infections in diabetic patients are difficult to treat and heal. To explore the effects of betaine ointment (BO) in promoting the healing of skin wounds and reducing the inflammation and apoptosis of skin cells in microbially infected diabetic mice. By detecting the minimum inhibitory concentrations (MICs) of betaine and plant monomer components such as psoralen, we prepared BO with betaine as the main ingredient, blended it with traditional Chinese medicines such as gromwell root and psoralen, and evaluated its antibacterial effects and safety in vitro and in vivo. The skin infection wound models of ordinary mice and diabetic mice were constructed, and the OTC drugs mupirocin ointment and Zicao ointment were used as controls to evaluate the antibacterial effects in vivo and the anti-inflammatory and anti-apoptotic effects of BO. The MICs of betaine against microorganisms such as Staphylococcus aureus (S. aureus), Candida albicans and Cryptococcus neoformans ranged from 4 to 32 μg/mL. Gromwell root and psoralea, both of which contain antimicrobial components, mixed to prepare BO with MICs ranging from 16 to 64 μg/mL, which is 32-256 times lower than those of Zicao ointment, although the MIC is greater than that of betaine. After 15 days of treatment with BO for USA300-infected ordinary mice, the wound scab removal rates were 83.3%, while those of mupirocin ointment and Zicao ointment were 66.7% and 0%, respectively, and the differences were statistically significant. In diabetic mice, the wound scab removal rate of BO and mupirolacin ointment was 80.0%, but BO reduced wound inflammation and the apoptosis of skin cells and facilitated wound healing. The ointment prepared by mixing betaine and traditional Chinese medicine can effectively inhibit common skin microorganisms and has a strong effect on the skin wounds of sensitive or drug-resistant S. aureus-infected ordinary mice and diabetic mice.

Exploring Metal Ions as Potential Antimicrobial Agents to Combat Future Drug Resistance in Mycoplasma bovis

The rise in antimicrobial resistance (AMR) in Mycoplasma bovis underscores the urgent need for alternative treatments. This study evaluated the minimal inhibitory concentrations (MICs) of four metal ions (cobalt, copper, silver, and zinc) and colloidal silver against 15 clinical M. bovis isolates, alongside conventional antimicrobials (florfenicol, tetracycline, tulathromycin, and tylosin). Colloidal silver demonstrated the most effective antimicrobial activity, inhibiting 81.25% of isolates at 1.5 mg/L, while silver inhibited 93.7% of isolates at concentrations above 1.5 mg/L. Copper exhibited notable efficacy, inhibiting 37.5% of isolates at 1.5 mg/L, with a small proportion responding at 0.1 mg/L. Cobalt and zinc displayed variable activity, with MIC values ranging from 0.7 to 12.5 mg/L. In contrast, conventional antimicrobials showed limited effectiveness: tetracycline inhibited 31.25% of isolates at ≥16 mg/L, tylosin inhibited 25% at 16 mg/L, and tulathromycin MICs ranged from 0.5 to 8 mg/L. Time–kill assays revealed a reduction in M. bovis viability after eight hours of exposure to silver and colloidal silver, though higher concentrations (4×–8× MIC) were required for complete eradication. These findings highlight the significant potential of colloidal silver and copper as alternatives for treating M. bovis infections and combating AMR. Further research is essential to explore their standalone and synergistic applications for therapeutic use.

Deep eutectic solvent enhances antibacterial activity of a modular lytic enzyme against Acinetobacter baumannii

In this study, we evaluated the combined effect between MLE-15, a modular lytic enzyme composed of four building blocks, and reline, a natural deep eutectic solvent. The bioinformatic analysis allowed us to determine the spatial architecture of MLE-15, whose components were bactericidal peptide cecropin A connected via a flexible linker to the cell wall binding domain (CBD) of mesophilic 201ϕ2 − 1 endolysin and catalytic domain (EAD) of highly thermostable Ph2119 endolysin. The modular enzyme showed high thermostability with the melting temperature of 93.97 ± 0.38 °C, significantly higher than their natural counterparts derived from mesophilic sources. The minimum inhibitory concentration (MIC) of MLE-15 was 100 µg/mL for a panel of Gram-positive and Gram-negative bacteria, while the MIC of reline ranged from 6.25 to 25% v/v for the same strains. The addition of reline effectively reduced the MIC of MLE-15 from 100 µg/mL to 3.15–50 µg/mL. This combination displayed additive effects for most strains and synergism for extensively antibiotic-resistant Acinetobacter baumannii and Bacillus subtilis. The subsequent evaluation revealed that MLE-15 eliminated planktonic cells of A. baumannii RUH134, but was ineffective against matured biofilms. However, combined with reline, MLE-15 reduced the bacterial load in the matured biofilm by 1.39 log units. Confocal fluorescence microscopy indicated that reline damaged the structure of the biofilm, allowing MLE-15 to penetrate it. Additionally, MLE-15 and its combination with reline eradicated meropenem-persistent cells of A. baumannii RUH134. Effectiveness in lowering the MIC value of MLE-15 as well as protection against antibiotic-tolerant persister cells, indicate that MLE-15 and reline combination is a promising candidate for effective therapies in bacterial infections, which is especially important in the light of the global crisis of antimicrobial resistance.

Analysis of Antimicrobial Activity of Extracts From Leaves of anacardium occidentale l. (cashew) Front of Clinical Isolated from Gram-Negative Bacteria Resistant to Antibiotics

Objective: The aim of this study was to analyze the chemical composition of the hydroalcoholic extract of Anacardium occidentale L. (cashew) and the antimicrobial activity of this antibiotic against resistant gram-negative bacteria (GNB). Theoretical Framework: The spread of resistant microorganisms to available chemotherapeutic drugs is a major public health problem and points to the need for research into new antimicrobials. Plants, due to their secondary metabolism, produce compounds of biological importance, being an important source of bioprospection. Method: The collected leaves were dried at 37 °C, ground and soaked in 70% ethanol-water solution at a ratio drug / solvent of 1: 5 for seven days. After this time the mash was filtered and dried at 40 °C in a water bath until completely dry and obtain of the dry extract. The phytochemical analysis was based on the qualitative determination of saponins, alkaloids, flavonoids, steroids / triterpenoids and tannins. The study of the susceptibility of the BGN extract was determined by the technique of REMA (Resazurin Microtiter Assay), using the minimum inhibitory concentration (MIC). The maintenance of the blue or pink color in the wells of the plate was interpreted, respectively, as the presence and absence of microbial growth. Results and Discussion: Phytochemicals in trials observed the presence of saponins, flavonoids and tannins and analysis of antimicrobial activity results demonstrated weak antimicrobial activity against most of the microorganisms evaluated, except for Pseudomonas sp. (7370) that showed MIC of 250µg/mL. Research Implications: Quantitative methods are necessary to better assess and quantify the secondary metabolites of the Anacardium occidentale L. in the region.

Phytochemical Screening, Antioxidant and Antibacterial Properties of Alcoholic Extract of Saussurea costus Roots

Background: Diseases in their essence are non-curable and the underlying pathogenesis is bidirectional of inflammation and oxidative stress. Fighting oxidative stress and inflammation should be the target for any first-line therapy, perhaps via chemical or herbal therapy. In the present study, we aimed to identify the antioxidant and antibacterial activities of Saussurea costus roots. The study aimed to harness S. costus plant as antimicrobial via assessment of its antibacterial efficacy against pathogens by disc diffusion and minimum inhibitory concentration (MIC) tests. Methods: Alcoholic extract of S. costus roots was tested for antioxidant activity using diphenyl picrylhydrazyl (DPPH) and antibacterial effects on a few common bacterial species (Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Proteus spp.). Result: The contents of S. costus extracts revealed of the presence of therapeutic principle components with variety of medicinal effects, including alkaloids, terpenoid, phenols and others. Different concentration of extracts have comparable antioxidant activity to ascorbic acid (81.96%). Similarly, different concentrations of the extract have confirmed antibacterial activity against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli with no impacts on Proteus spp.