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Molecules (Basel, Switzerland) Jun 2024This study presents fibers based on methacrylic acid-methyl methacrylate (Eudragit L100) as Cu(II) adsorbents, resulting in antimicrobial complexes. Eudragit L100, an...
This study presents fibers based on methacrylic acid-methyl methacrylate (Eudragit L100) as Cu(II) adsorbents, resulting in antimicrobial complexes. Eudragit L100, an anionic copolymer synthesized by radical polymerization, was electrospun in dimethylformamide (DMF) and ethanol (EtOH). The electrospinning process was optimized through a 2-factorial design, with independent variables (copolymer concentration and EtOH/DMF volume ratio) and three repetitions at the central point. The smallest average fiber diameter (259 ± 53 nm) was obtained at 14% / Eudragit L100 and 80/20 EtOH/DMF volume ratio. The fibers were characterized using scanning electron microscopy (SEM), infrared spectroscopy in attenuated total reflectance mode (FTIR-ATR), and differential scanning calorimetry (DSC). The pseudo-second-order mechanism explained the kinetic adsorption toward Cu(II). The fibers exhibited a maximum adsorption capacity (q) of 43.70 mg/g. The DSC analysis confirmed the Cu(II) absorption, indicating complexation between metallic ions and copolymer networks. The complexed fibers showed a lower degree of swelling than the non-complexed fibers. The complexed fibers exhibited bacteriostatic activity against Gram-negative () and Gram-positive () bacteria. This study successfully optimized the electrospinning process to produce thin fibers based on Eudragit L100 for potential applications as adsorbents for Cu(II) ions in aqueous media and for controlling bacterial growth.
Topics: Copper; Polymethacrylic Acids; Anti-Infective Agents; Adsorption; Spectroscopy, Fourier Transform Infrared; Staphylococcus aureus; Methacrylates; Kinetics; Calorimetry, Differential Scanning; Microbial Sensitivity Tests
PubMed: 38930901
DOI: 10.3390/molecules29122835 -
Molecules (Basel, Switzerland) Jun 2024The current study was designed to uncover the chemistry and bioactivity potentials of growing wild in Jordan. In this context, the fresh aerial parts obtained from the...
The current study was designed to uncover the chemistry and bioactivity potentials of growing wild in Jordan. In this context, the fresh aerial parts obtained from the plant material were subjected to hydrodistillation followed by GC/MS analysis. The main components of the HDEO were γ-patchoulene (23.79%), β-dihydro agarofuran (23.50%), α-guaiene (14.11%), and valencene (13.28%). Moreover, the crude thanolic extract was partitioned to afford two main major fractions, the aqueous methanol (BLM) and butanol (BLB). Phytochemical investigation of both fractions, using conventional chromatographic techniques followed by careful inspection of the spectral data for the isolated compounds (NMR, IR, and UV-Vis), resulted in the characterization of five known compounds, including α-spinasteryl (), ethyl arachidate (), ethyl myristate (), quercetin-3--β-d-glucopyranosyl-(1-4")-α-L-rhamnopyranosyl (), and isorhamnetin-3--β-d-glucopyranosyl-(1-4")-α-L-rhamnopyranosyl (). The TPC, TFC, and antioxidant activity testing of both fractions and HDEO revealed an interesting ABTS scavenging potential of the BLB fraction compared to the employed positive controls, which is in total agreement with its high TP and TF contents. Cytotoxic evaluation tests revealed that BLM had interesting cytotoxic effects on the normal breast cell line MDA-MB-231 (ATCC-HTB-26) and the normal dermal fibroblast (ATCC PCS-201-012) and normal African green monkey kidney Vero (ATCC-CCL-81) cell lines. Despite both the BLB and BLM fractions showing interesting AChE inhibition activities (IC = 217.9 ± 5.3 µg/mL and 139.1 ± 5.6 µg/mL, respectively), the HDEO revealed an interestingly high AChE inhibition power (43.8 ± 2.7 µg/mL) that far exceeds the one observed for galanthamine (91.4 ± 5.2 µg/mL). The HDEO, BLM, and BLB exhbitied no interesting antimicrobial activity against , , , , or .
Topics: Jordan; Plant Extracts; Antioxidants; Animals; Bupleurum; Humans; Vero Cells; Phytochemicals; Chlorocebus aethiops; Cell Line, Tumor; Plant Components, Aerial; Gas Chromatography-Mass Spectrometry; Cell Survival; Antineoplastic Agents, Phytogenic
PubMed: 38930796
DOI: 10.3390/molecules29122730 -
Microorganisms Jun 2024The World Health Organization (WHO) has prioritized developing new drugs against specific bacteria and fungi, such as and spp. While is commonly called the...
The World Health Organization (WHO) has prioritized developing new drugs against specific bacteria and fungi, such as and spp. While is commonly called the "cure-everything", its scientifically proven benefits are limited to anti-inflammatory and antioxidant actions. Therefore, this study aims to determine the spectrum of antimicrobial activity of and assess its cytotoxicity. Thus, broth microdilution test was conducted according to the CLSI M7-A9 and M27-A3 reference methods. After screening, microbial species with minimum inhibitory concentration (MIC) values were selected for biofilm tests. These tests evaluated biomass using the crystal violet (CV) test, metabolic activity using the MTT assay, and structural analysis via Scanning Electron Microscopy (SEM). Cytotoxicity was evaluated in human gingival fibroblasts (FMM-1). There were reductions of 29.4 and 42.7% in CV and MTT assays for spp. biofilm. and biofilms showed a decrease of 15.7 and 28.6%, respectively. Cell viability tests indicated 55.1, 56.9, and 65.5% of viability after contact with 1.93, 0.96, and 0.48 mg/mL of the extract, respectively. The extract showed antimicrobial action, displayed MIC values, and antibiofilm action on , and . The cytotoxicity on the FMM-1 cell line was dose-dependent. Therefore, extract holds significant potential for developing new drugs.
PubMed: 38930547
DOI: 10.3390/microorganisms12061165 -
Microorganisms May 2024aeruginosa is a pathogen that causes healthcare-associated infections (HAIs) worldwide. It is unclear whether isolated from the natural environment has the same...
aeruginosa is a pathogen that causes healthcare-associated infections (HAIs) worldwide. It is unclear whether isolated from the natural environment has the same pathogenicity and antimicrobial resistance potential as clinical strains. In this study, virulence- and resistance-associated genes were compared in 14 genomic sequences of clinical and environmental isolates of using the VFDB, PATRIC, and CARD databases. All isolates were found to share 62% of virulence genes related to adhesion, motility, secretion systems, and quorum sensing and 72.9% of resistance genes related to efflux pumps and membrane permeability. Our results indicate that both types of isolates possess conserved genetic information associated with virulence and resistance mechanisms regardless of the source. However, none of the environmental isolates were associated with high-risk clones (HRCs). These clones (ST235 and ST111) were found only in clinical isolates, which have an impact on human medical epidemiology due to their ability to spread and persist, indicating a correlation between the clinical environment and increased virulence. The genomic variation and antibiotic susceptibility of environmental isolates of suggest potential biotechnological applications if obtained from sources that are under surveillance and investigation to limit the emergence and spread of antibiotic resistant strains.
PubMed: 38930498
DOI: 10.3390/microorganisms12061116 -
Antioxidants (Basel, Switzerland) May 2024() is an opportunistic pathogen frequently isolated from cutaneous chronic wounds. How , in the presence of oxidative stress (OS), colonizes chronic wounds and forms a...
() is an opportunistic pathogen frequently isolated from cutaneous chronic wounds. How , in the presence of oxidative stress (OS), colonizes chronic wounds and forms a biofilm is still unknown. The purpose of this study is to investigate the changes in gene expression seen when PA is challenged with the high levels of OS present in chronic wounds. We used a biofilm-forming strain isolated from the chronic wounds of our murine model (RPA) and performed a qPCR to obtain gene expression patterns as RPA developed a biofilm in vitro in the presence of high levels of OS, and then compared the findings in vivo, in our mouse model of chronic wounds. We found that the planktonic bacteria under OS conditions overexpressed quorum sensing genes that are important for the bacteria to communicate with each other, antioxidant stress genes important to reduce OS in the microenvironment for survival, biofilm formation genes and virulence genes. Additionally, we performed RNAseq in vivo and identified the activation of novel genes/pathways of the Type VI Secretion System (T6SS) involved in RPA pathogenicity. In conclusion, RPA appears to survive the high OS microenvironment in chronic wounds and colonizes these wounds by turning on virulence, biofilm-forming and survival genes. These findings reveal pathways that may be promising targets for new therapies aimed at disrupting -containing biofilms immediately after debridement to facilitate the treatment of chronic human wounds.
PubMed: 38929094
DOI: 10.3390/antiox13060655 -
International Journal of Environmental... May 2024The effects of exposure to airborne particulate matter with a size of 10 μm or less (PM) on C57BL/6 mouse corneas, their response to (PA) infection, and the protective...
The effects of exposure to airborne particulate matter with a size of 10 μm or less (PM) on C57BL/6 mouse corneas, their response to (PA) infection, and the protective effects of SKQ1 were determined. C57BL/6 mouse corneas receiving PBS or SKQ1 were exposed to control (air) or PM for 2 weeks, infected, and the disease was documented by clinical score, PMN quantitation, bacterial plate count, RT-PCR and Western blot. PBS-treated, PM-exposed corneas did not differ at 1 day postinfection (dpi), but exhibited earlier (3 dpi) corneal thinning compared to controls. By 3 dpi, PM significantly increased corneal mRNA levels of several pro-inflammatory cytokines, but decreased IL-10, NQO1, GR1, GPX4, and Nrf2 over control. SKQ1 reversed these effects and Western blot selectively confirmed the RT-PCR results. PM resulted in higher viable bacterial plate counts at 1 and 3 dpi, but SKQ1 reduced them at 3 dpi. PM significantly increased MPO in the cornea at 3 dpi and was reduced by SKQ1. SKQ1, used as an adjunctive treatment to moxifloxacin, was not significantly different from moxifloxacin alone. Exposure to PM increased the susceptibility of C57BL/6 to PA infection; SKQ1 significantly reversed these effects, but was not effective as an adjunctive treatment.
Topics: Animals; Mice, Inbred C57BL; Pseudomonas Infections; Particulate Matter; Pseudomonas aeruginosa; Mice; Cornea; Disease Susceptibility; Cytokines; Female; Air Pollutants
PubMed: 38928968
DOI: 10.3390/ijerph21060722 -
International Journal of Molecular... Jun 2024This paper presents the work performed to transition a lab-scale synthesis (1 g) to a large-scale (400 g) synthesis of the 3-5-diamino-1H-Pyrazole Disperazol, a new...
This paper presents the work performed to transition a lab-scale synthesis (1 g) to a large-scale (400 g) synthesis of the 3-5-diamino-1H-Pyrazole Disperazol, a new pharmaceutical for treatment of antibiotic-resistant biofilm infections. The potentially hazardous diazotisation step in the lab-scale synthesis was transformed to a safe and easy-to-handle flow chemistry step. Additionally, the paper presents an OSHA-recommended safety assessment of active compound , as performed by Fauske and Associates, LLC, Burr Ridge, IL, USA.
Topics: Pyrazoles; Pseudomonas aeruginosa; Anti-Bacterial Agents; Biofilms; Humans; Pseudomonas Infections; Risk Assessment
PubMed: 38928443
DOI: 10.3390/ijms25126737 -
Genes Jun 2024Many enzymes in the Raetz pathway for lipid A biosynthesis in are essential. A homologous protein Pa1792|LpxH in is known to complement the loss of LpxH in ....
Many enzymes in the Raetz pathway for lipid A biosynthesis in are essential. A homologous protein Pa1792|LpxH in is known to complement the loss of LpxH in . Genome-wide transposon-insertion sequencing analysis indicates that is essential in . However, genetic analysis of in has not been carried out, partly because the conditional alleles of essential genes are not readily constructed. In this study, we first constructed a plasmid-based temperature-sensitive mutant or in PAO1. Spot-plating assay indicated that was lethal at a restrictive temperature, confirming its essentiality for growth. Microscopic analysis revealed that exhibited an oval-shaped morphology, suggesting that was required for rod-shape formation. SDS-PAGE and Western blotting analysis showed that failed to synthesize lipid A, consistent with its function in lipid A biosynthesis. Strong expression of but not the non-homologous isoenzyme or impeded growth and caused cell lysis, implying that -specific cofactors were required for this toxic effect in . Together, our results demonstrate that is essential for lipid A biosynthesis, rod-shaped growth, and viability in . We propose that this plasmid-based conditional allele is a useful tool for the genetic study of essential genes in .
Topics: Pseudomonas aeruginosa; Plasmids; Bacterial Proteins; Temperature; Mutation; Lipid A; Escherichia coli
PubMed: 38927720
DOI: 10.3390/genes15060784 -
Biology May 2024Compared to pathogens and , HYS has stronger virulence towards . However, the underlying mechanisms haven't been fully understood. The heme synthesis system is...
Compared to pathogens and , HYS has stronger virulence towards . However, the underlying mechanisms haven't been fully understood. The heme synthesis system is essential for virulence, and former studies of HemN have focused on the synthesis of heme, while the relationship between HemN and virulence were barely pursued. In this study, we hypothesized that deficiency affected 7-hydroxytropolone (7-HT) biosynthesis and redox levels, thereby reducing bacterial virulence. There are four genes in HYS, and we reported for the first time that deletion of significantly reduced the virulence of HYS towards , whereas the reduction in virulence by the other three genes was not significant. Interestingly, deletion significantly reduced colonization of HYS in the gut of . Further studies showed that HemN2 was regulated by GacS and participated in the virulence of HYS towards by mediating the synthesis of the virulence factor 7-HT. In addition, HemN2 and GacS regulated the virulence of HYS by affecting antioxidant capacity and nitrative stress. In short, the findings that HemN2 was regulated by the Gac system and that it was involved in bacterial virulence via regulating 7-HT synthesis and redox levels were reported for the first time. These insights may enlighten further understanding of HemN-based virulence in the genus .
PubMed: 38927253
DOI: 10.3390/biology13060373 -
Antibiotics (Basel, Switzerland) Jun 2024We evaluated the activities of aztreonam/avibactam and recently approved β-lactamase inhibitor combinations (BLICs) to compare the antimicrobial susceptibility patterns...
Activity of Aztreonam/Avibactam and Recently Approved β-Lactamase Inhibitor Combinations against Enterobacterales and from Intensive Care Unit and Non-Intensive Care Unit Patients.
We evaluated the activities of aztreonam/avibactam and recently approved β-lactamase inhibitor combinations (BLICs) to compare the antimicrobial susceptibility patterns of Enterobacterales and isolated from intensive care unit (ICU) and non-ICU patients. Clinical isolates (1/patient) were consecutively collected from 72 United States medical centres in 2020-2022 and susceptibility tested by broth microdilution. The results for 5421 isolates from ICU patients were analysed and compared to those for 20,649 isolates from non-ICU patients. Isolates from ventilator-associated pneumonia patients were analysed separately. Aztreonam/avibactam inhibited 100.0%/>99.9% Enterobacterales and 100.0%/98.3% of carbapenem-resistant Enterobacterales (CRE) from ICU/non-ICU patients at ≤8 mg/L, respectively. The CRE susceptibility rates were 88.5%/82.9% for ceftazidime/avibactam, 82.1%/81.2% for meropenem/vaborbactam, and 78.2%/72.6% for imipenem/relebactam among ICU/non-ICU isolates. Among the isolates from ICU/non-ICU patients, the susceptibility rates were 96.3%/97.6% for ceftazidime/avibactam, 97.2/98.4% for ceftolozane/tazobactam, 97.1%/98.0% for imipenem/relebactam, 77.8%/84.6% for piperacillin/tazobactam, and 76.9%/85.8% for meropenem; aztreonam/avibactam inhibited 78.0%/81.9% of at ≤8 mg/L. In summary, lower susceptibility rates were observed among ICU than non-ICU isolates. Aztreonam/avibactam exhibited potent in vitro activity and broad-spectrum activity against Enterobacterales from ICU and non-ICU patients, including CRE and isolates non-susceptible to newer BLICs. Against , aztreonam/avibactam showed a spectrum of activity comparable to that of piperacillin/tazobactam, meropenem, and ceftazidime.
PubMed: 38927230
DOI: 10.3390/antibiotics13060564