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1.
Braz J Biol ; 84: e284085, 2024.
Article in English | MEDLINE | ID: mdl-38958299

ABSTRACT

The current study evaluates the antibacterial activity of Camponotus compressus (Hymenoptera: Formicidae) body crude extracts. The increasing antibiotic resistance of bacteria has prompted the world to turn its attention towards insects in the search for new sources of antibacterial compounds. The body crude extract obtained with different solvents were tested against both Gram positive (Staphylococcus aureus, Bacillus subtilis) and Gram negative bacteria (Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae). Standard disc diffusion method was used to perform the activity. The extracts of C. compressus were investigated for their effectiveness against all resistant pathogenic bacteria. Staphylococcus aureus was found to be the most susceptible, exhibiting a high average growth inhibition, while Bacillus subtilis showed a lower average growth inhibition zone. Our findings regarding the inhibitory effect of C. compressus extracts show the presence of a broad-spectrum antibacterial compound. This will be helpful in the search for novel natural antibiotics against robust pathogenic bacterial strains.


Subject(s)
Anti-Bacterial Agents , Ants , Gram-Negative Bacteria , Gram-Positive Bacteria , Microbial Sensitivity Tests , Animals , Anti-Bacterial Agents/pharmacology , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Ants/drug effects , Complex Mixtures/pharmacology
2.
New Microbiol ; 47(2): 146-151, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39023523

ABSTRACT

In the present retrospective study, we have evaluated bacterial pathogens isolated from patients admitted to the Burn Care Unit at the Military Medical Academy, Varna, Bulgaria over a three-year period (January 2019 - December 2021). We also tried to summarize the corresponding antibiotic resistance pattern of the isolated infectious agents. A total of 1030 isolates were obtained from 1912 burn wound samples investigated. There were 553 Gram-positive (53.7%) and 477 Gram-negative (46.3%) isolates. The most common isolates for the study period were coagulase-negative staphylococci (CoNS) (25%), Pseudomonas aeruginosa (17.7%), Staphylococcus aureus (16.6%), Acinetobacter baumannii (7.7%), Enterobacter spp. (7.1%), Escherichia coli (4.4%), Proteus spp. (3.4%), and Klebsiella spp. (2.9%). Glycopeptide antibiotics and linezolid were the most effective drugs against gram-positive isolates, followed by amikacin (for synergistic combinations), whereas colistin, imipenem, meropenem, cefoperazon/sulbactam, and piperacillin/tazobactam were the most active drugs against Gram-negative isolates, and colistin, ampicillin/sulbactam - against A. baumannii.


Subject(s)
Anti-Bacterial Agents , Burns , Microbial Sensitivity Tests , Wound Infection , Bulgaria/epidemiology , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Burns/microbiology , Burns/complications , Retrospective Studies , Wound Infection/microbiology , Wound Infection/drug therapy , Drug Resistance, Bacterial , Bacteria/drug effects , Bacteria/isolation & purification , Bacteria/classification , Gram-Negative Bacteria/drug effects , Gram-Negative Bacteria/isolation & purification , Hospitalization , Gram-Positive Bacteria/drug effects , Gram-Positive Bacteria/isolation & purification , Female , Male
3.
Carbohydr Polym ; 342: 122340, 2024 Oct 15.
Article in English | MEDLINE | ID: mdl-39048188

ABSTRACT

The present study reports on the valorisation of starch waste biomass to produce dual-active cryogels and hydrogels able to adsorb water and deliver antimicrobial substances for fresh food packaging applications. Starch hydrogels were prepared by oxidation with sodium metaperiodate in water and mild conditions, while cryogels were obtained by freeze-drying process. To explore the role of starch composition on the final properties of materials, two starches differing in amylose/amylopectin ratio, were evaluated. The prepared materials were microstructurally and morphologically characterized by FTIR and NMR spectroscopy (1D, 2D, and DOSY experiments), and SEM microscopy. To provide the materials with active properties, they were loaded with antimicrobial molecules by absorption, or by crosslinking via Schiff-base reaction. All materials demonstrated high water absorption capacity and ability to deliver volatile molecules, including diacetyl and complex mixtures like mint essential oil. The release profiles of the adsorbed molecules were determined through quantitative NMR spectroscopy over time. The antibacterial activity was successfully demonstrated against Gram-positive bacterial strains for unloaded cryogels and hydrogels, and after loading with diacetyl and essential oil. The developed materials can be regarded as part of active pads for food packaging applications capable to control moisture inside the package and inhibit microbial contamination.


Subject(s)
Anti-Bacterial Agents , Cryogels , Food Packaging , Hydrogels , Starch , Food Packaging/methods , Cryogels/chemistry , Hydrogels/chemistry , Hydrogels/pharmacology , Starch/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Microbial Sensitivity Tests , Gram-Positive Bacteria/drug effects , Water/chemistry
4.
Carbohydr Polym ; 342: 122389, 2024 Oct 15.
Article in English | MEDLINE | ID: mdl-39048229

ABSTRACT

The paper reports new hydrogels based on quaternary ammonium salts of chitosan designed as biocidal products. The chitosan derivative was crosslinked with salicylaldehyde via reversible imine bonds and supramolecular self-assemble to give dynamic hydrogels which respond to environmental stimuli. The crosslinking mechanism was demonstrated by 1H NMR and FTIR spectroscopy, and X-ray diffraction and polarized light microscopy. The hydrogel nature, self-healing and thixotropy were proved by rheological investigation and visual observation, and their morphology was assessed by scanning electron microscopy. The relevant properties for application as biocidal products, such as swelling, dissolution, bioadhesiveness, antimicrobial activity and ex-vivo hemocompatibility and in vivo local toxicity and biocompatibility on experimental mice were measured and analyzed in relationship with the imination degree and the influence of each component. It was found that the hydrogels are superabsorbent, have good adhesivity to skin and various surfaces and antimicrobial activity against relevant gram-positive and gram-negative bacteria, while being hemocompatible and biocompatible. Besides, the hydrogels are easily biodegraded in soil. All these properties recommend the studied hydrogels as ecofriendly biocidal agents for living tissues and surfaces, but also open the perspectives of their use as platform for in vivo applications in tissue engineering, wound healing, or drug delivery systems.


Subject(s)
Biocompatible Materials , Chitosan , Hydrogels , Quaternary Ammonium Compounds , Chitosan/chemistry , Chitosan/pharmacology , Hydrogels/chemistry , Hydrogels/pharmacology , Quaternary Ammonium Compounds/chemistry , Quaternary Ammonium Compounds/pharmacology , Animals , Biocompatible Materials/pharmacology , Biocompatible Materials/chemistry , Mice , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Microbial Sensitivity Tests , Disinfectants/pharmacology , Disinfectants/chemistry , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Aldehydes
5.
BMC Microbiol ; 24(1): 262, 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39026170

ABSTRACT

BACKGROUND: The ineffectiveness of treatments for infections caused by biofilm-producing pathogens and human carcinoma presents considerable challenges for global public health organizations. To tackle this issue, our study focused on exploring the potential of synthesizing new complexes of Co(II), Cu(II), Ni(II), and Zn(II) with sorbic acid to enhance its antibacterial, antibiofilm, and anticancer properties. METHODS: Four novel complexes were synthesized as solid phases by reacting sorbic acid with Co(II), Cu(II), Ni(II), and Zn(II). These complexes were characterized by various technique, including infrared spectra, UV-Visible spectroscopy, proton nuclear magnetic resonance (1H NMR), and thermal analysis techniques, including thermogravimetry (TG). RESULTS: The data acquired from all investigated chemical characterization methods confirmed the chemical structure of the sorbate metal complexes. These complexes exhibited antibacterial and antibiofilm properties against both Gram-positive and Gram-negative bacteria. Furthermore, these complexes enhanced the antibacterial effects of commonly used antibiotics, such as gentamicin and imipenem, with fractional inhibitory concentration (FIC) indices ≤ 0.5. Notably, the Cu(II) complex displayed the most potent antibacterial and antibiofilm activities, with minimum inhibitory concentration (MIC) values of 312.5 µg/mL and 625.0 µg/mL for Bacillus cereus and Escherichia coli, respectively. Additionally, in vitro assays using the methyl thiazolyl tetrazolium (MTT) method showed inhibitory effects on the growth of the human colon carcinoma cell line (HCT-116 cells) following treatment with the investigated metal complexes. The IC50 values for Co(II), Cu(II), Zn(II), and Ni(II) were 3230 µg/mL, 2110 µg/mL, 3730 µg/mL, and 2240 µg/mL, respectively. CONCLUSION: Our findings offer potential for pharmaceutical companies to explore the development of novel combinations involving traditional antibiotics or anticancer drugs with sorbate copper complex.


Subject(s)
Anti-Bacterial Agents , Antineoplastic Agents , Biofilms , Coordination Complexes , Microbial Sensitivity Tests , Biofilms/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Coordination Complexes/pharmacology , Coordination Complexes/chemistry , Coordination Complexes/chemical synthesis , Sorbic Acid/pharmacology , Sorbic Acid/chemistry , Gram-Positive Bacteria/drug effects , Gram-Negative Bacteria/drug effects , Cell Line, Tumor , Cell Survival/drug effects
6.
Cell Biochem Funct ; 42(5): e4093, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38978319

ABSTRACT

The main objective of the study is to evaluate the antioxidant, anticancer, and antimicrobial activities of Anchusa officinalis L. in vitro and in silico. The dried aerial parts of A. officinalis L. were extracted with methanol. Total phenolic and flavonoid content was analyzed. Antioxidant and antimicrobial effects were tested against both gram-positive and gram-negative bacteria. Gas chromatography-mass spectrometry analysis revealed the presence of 10 phytochemical compounds, and cyclobutane (26.07%) was identified as the major photochemical compound. The methanol extract exhibited the maximum amount of total phenolic content (118.24 ± 4.42 mg QE/g dry weight of the dry extract) (R2 = 0.994) and the total flavonoid content was 94 ± 2.34 mg QE/g dry weight of the dry extract (R2 = 0.999). The IC50 value for 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid was 107.12 ± 3.42 µg/mL, and it was high for 1,1-diphenyl-2-picryl hydrazyl (123.94 ± 2.31 µg/mL). The IC50 value was 72.49 ± 3.14 against HepG2 cell lines, and a decreased value was obtained (102.54 ± 4.17 g/mL) against MCF-7 cell lines. The methanol extract increased the expression of caspase mRNA and Bax mRNA levels when compared to the control experiment (p < .05). The conclusions, A. officinalis L. aerial parts extract exhibited antibacterial, antifungal, and antioxidant activities.


Subject(s)
Antioxidants , Methanol , Plant Components, Aerial , Plant Extracts , Plant Extracts/pharmacology , Plant Extracts/chemistry , Humans , Plant Components, Aerial/chemistry , Antioxidants/pharmacology , Antioxidants/chemistry , Antioxidants/isolation & purification , Methanol/chemistry , Microbial Sensitivity Tests , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/isolation & purification , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , MCF-7 Cells , Computer Simulation , Flavonoids/pharmacology , Flavonoids/chemistry , Phenols/pharmacology , Phenols/chemistry , Apoptosis/drug effects
7.
Molecules ; 29(13)2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38998972

ABSTRACT

Heterocyclic compounds, particularly those containing azole rings, have shown extensive biological activity, including anticancer, antibacterial, and antifungal properties. Among these, the imidazole ring stands out due to its diverse therapeutic potential. In the presented study, we designed and synthesized a series of imidazole derivatives to identify compounds with high biological potential. We focused on two groups: thiosemicarbazide derivatives and hydrazone derivatives. We synthesized these compounds using conventional methods and confirmed their structures via nuclear magnetic resonance spectroscopy (NMR), MS, and elemental analysis, and then assessed their antibacterial and antifungal activities in vitro using the broth microdilution method against Gram-positive and Gram-negative bacteria, as well as Candida spp. strains. Our results showed that thiosemicarbazide derivatives exhibited varied activity against Gram-positive bacteria, with MIC values ranging from 31.25 to 1000 µg/mL. The hydrazone derivatives, however, did not display significant antibacterial activity. These findings suggest that structural modifications can significantly influence the antimicrobial efficacy of imidazole derivatives, highlighting the potential of thiosemicarbazide derivatives as promising candidates for further development in antibacterial therapies. Additionally, the cytotoxic activity against four cancer cell lines was evaluated. Two derivatives of hydrazide-hydrazone showed moderate anticancer activity.


Subject(s)
Anti-Bacterial Agents , Antifungal Agents , Antineoplastic Agents , Gram-Positive Bacteria , Microbial Sensitivity Tests , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antifungal Agents/pharmacology , Antifungal Agents/chemical synthesis , Antifungal Agents/chemistry , Gram-Positive Bacteria/drug effects , Nitroimidazoles/pharmacology , Nitroimidazoles/chemistry , Nitroimidazoles/chemical synthesis , Cell Line, Tumor , Gram-Negative Bacteria/drug effects , Structure-Activity Relationship , Semicarbazides/chemistry , Semicarbazides/pharmacology , Semicarbazides/chemical synthesis , Hydrazones/chemistry , Hydrazones/pharmacology , Hydrazones/chemical synthesis , Candida/drug effects , Molecular Structure
8.
Int J Mol Sci ; 25(13)2024 Jun 22.
Article in English | MEDLINE | ID: mdl-38999964

ABSTRACT

Keeping wounds clean in small animals is a big challenge, which is why they often become infected, creating a risk of transmission to animal owners. Therefore, it is crucial to search for new biocompatible materials that have the potential to be used in smart wound dressings with both wound healing and bacteriostatic properties to prevent infection. In our previous work, we obtained innovative hyaluronate matrix-based bionanocomposites containing nanosilver and nanosilver/graphene oxide (Hyal/Ag and Hyal/Ag/GO). This study aimed to thoroughly examine the bacteriostatic properties of foils containing the previously developed bionanocomposites. The bacteriostatic activity was assessed in vitro on 88 Gram-positive (n = 51) and Gram-negative (n = 37) bacteria isolated from wounds of small animals and whose antimicrobial resistance patterns and resistance mechanisms were examined in an earlier study. Here, 69.32% of bacterial growth was inhibited by Hyal/Ag and 81.82% by Hyal/Ag/GO. The bionanocomposites appeared more effective against Gram-negative bacteria (growth inhibition of 75.68% and 89.19% by Hyal/Ag and Hyal/Ag/Go, respectively). The effectiveness of Hyal/Ag/GO against Gram-positive bacteria was also high (inhibition of 80.39% of strains), while Hyal/Ag inhibited the growth of 64.71% of Gram-positive bacteria. The effectiveness of Hyal/Ag and Hyal/Ag/Go varied depending on bacterial genus and species. Proteus (Gram-negative) and Enterococcus (Gram-positive) appeared to be the least susceptible to the bionanocomposites. Hyal/Ag most effectively inhibited the growth of non-pathogenic Gram-positive Sporosarcina luteola and Gram-negative Acinetobacter. Hyal/Ag/GO was most effective against Gram-positive Streptococcus and Gram-negative Moraxella osloensis. The Hyal/Ag/GO bionanocomposites proved to be very promising new antibacterial, biocompatible materials that could be used in the production of bioactive wound dressings.


Subject(s)
Anti-Bacterial Agents , Graphite , Hyaluronic Acid , Metal Nanoparticles , Microbial Sensitivity Tests , Nanocomposites , Silver , Graphite/chemistry , Graphite/pharmacology , Nanocomposites/chemistry , Metal Nanoparticles/chemistry , Silver/chemistry , Silver/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Hyaluronic Acid/chemistry , Hyaluronic Acid/pharmacology , Animals , Gram-Negative Bacteria/drug effects , Gram-Negative Bacteria/growth & development , Gram-Positive Bacteria/drug effects , Gram-Positive Bacteria/growth & development , Wound Healing/drug effects , Bacteria/drug effects , Bacteria/growth & development
9.
PLoS One ; 19(7): e0306637, 2024.
Article in English | MEDLINE | ID: mdl-38985712

ABSTRACT

The Pelargonium genus encompasses around 280 species, most of which are used for medicinal purposes. While P. graveolens, P. odoratissimum, and P. zonale are known to exhibit antimicrobial activity, there is an evident absence of studies evaluating all three species to understand their chemical differences and biological effects. Through the analysis of the hydroalcoholic extracts of P. graveolens, P. odoratissimum, and P. zonale, using HPLC-DAD-MS/MS, quercetin and kaempferol derivatives were identified in these three species. Conversely, gallotannins and anthocyanins were uniquely detected in P. zonale. P. graveolens stood out due to the various types of myricetin derivatives that were not detected in P. odoratissimum and P. zonale extracts. Evaluation of their biological activities revealed that P. zonale displayed superior antibacterial and antibiofilm activities in comparison to the other two species. The antibacterial efficacy of P. zonale was observed towards the clinically relevant strains of Staphylococcus aureus ATCC 25923, Methicillin-resistant Staphylococcus aureus (MRSA) 333, Enterococcus faecalis ATCC 29212, and the Vancomycin-resistant E. faecalis INSPI 032. Fractionation analysis of P. zonale suggested that the antibacterial activity attributed to this plant is due to the presence of quercetin derivatives and kaempferol and its derivatives, alongside their synergistic interaction with gallotannins and anthocyanins. Lastly, the three Pelargonium species exhibited notable antioxidant activity, which may be attributed to their high content of total phenolic compounds.


Subject(s)
Anti-Bacterial Agents , Drug Resistance, Multiple, Bacterial , Pelargonium , Plant Extracts , Pelargonium/chemistry , Plant Extracts/pharmacology , Plant Extracts/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Drug Resistance, Multiple, Bacterial/drug effects , Microbial Sensitivity Tests , Chromatography, High Pressure Liquid , Gram-Positive Bacteria/drug effects , Tandem Mass Spectrometry , Biofilms/drug effects , Kaempferols/pharmacology , Kaempferols/chemistry , Kaempferols/metabolism , Quercetin/pharmacology , Quercetin/metabolism , Antioxidants/pharmacology , Antioxidants/chemistry
10.
Bioorg Med Chem Lett ; 110: 129878, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-38977107

ABSTRACT

A novel class of pleuromutilin derivatives possessing 1,2,3-triazole as the linker connected to phenyl analogues were designed. The antibacterial properties of the prepared compounds were assessed in vitro against five strains (E. coli, S. aureus, S. epidermidis, and E. faecalis). Most of the tested compounds displayed potent antibacterial activities against gram-positive bacteria and 14-O-[2-(4-((2,4-dinitrophenoxy)-methyl-1H-1,2,3-triazol-1-yl) acetamide)-2-methylpropan-2-yl) thioacetyl]mutilin (7c) exerted antibacterial activities against S. aureus, MRSA and S. epidermidis with MIC values 0.0625 µg/mL, representing 64-fold, 4-fold and 8-fold higher than tiamulin respectively. Compound 6e, 7c and 8c were chosen to carry out killing kinetics, which exhibited concentration-dependent effect. Subsequently, molecular modeling was conducted to further explore the binding of compound 6e, 7a, 7c, 8c and tiamulin with 50S ribosomal subunit from deinococcus radiodurans. The investigation revealed that the main interactions between compound 7c and the ribosomal residues were three hydrogen bonds, π-π, and p-π conjugate effects. Additionally, the free binding energy and docking score of 7c with the ribosome demonstrated the lowest values of -11.90 kcal/mol and -7.97 kcal/mol, respectively, consistent with its superior antibacterial activities.


Subject(s)
Anti-Bacterial Agents , Diterpenes , Microbial Sensitivity Tests , Pleuromutilins , Polycyclic Compounds , Triazoles , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Polycyclic Compounds/chemistry , Polycyclic Compounds/pharmacology , Diterpenes/pharmacology , Diterpenes/chemistry , Diterpenes/chemical synthesis , Triazoles/chemistry , Triazoles/pharmacology , Triazoles/chemical synthesis , Structure-Activity Relationship , Gram-Positive Bacteria/drug effects , Molecular Docking Simulation , Molecular Structure , Escherichia coli/drug effects , Staphylococcus epidermidis/drug effects , Staphylococcus aureus/drug effects , Dose-Response Relationship, Drug , Drug Discovery
11.
Bioorg Med Chem Lett ; 110: 129881, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-38996936

ABSTRACT

The direct-linked coumarin-benzimidazole hybrids, featuring aryl and n-butyl substituents at the N1-position of benzimidazole were synthesized through a Knoevenagel condensation reaction. This reaction involved the condensation of 1,2-diaminobenzene derivatives with coumarin-3-carboxylic acids in the presence of polyphosphoric acid (PPA) at 154 °C. The in vitro antibacterial potency of the hybrid molecules against different gram-positive and gram-negative bacterial strains led to the identification of the hybrids 6m and 6p with a MIC value of 6.25 µg/mL against a gram-negative bacterium, Klebsiella pneumonia ATCC 27736. Cell viability studies on THP-1 cells demonstrated that the compounds 6m and 6p were non-toxic at a concentration of 50 µM. Furthermore, in vivo efficacy studies using a murine neutropenic thigh infection model revealed that both compounds significantly reduced bacterial (Klebsiella pneumonia ATCC 27736) counts (more than 2 log) compared to the control group. Additionally, both compounds exhibited favorable physicochemical properties and drug-likeness characteristics. Consequently, these compounds hold promise as lead candidates for further development of effective antibacterial drugs.


Subject(s)
Anti-Bacterial Agents , Benzimidazoles , Coumarins , Microbial Sensitivity Tests , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Benzimidazoles/chemistry , Benzimidazoles/pharmacology , Benzimidazoles/chemical synthesis , Coumarins/chemistry , Coumarins/pharmacology , Coumarins/chemical synthesis , Animals , Mice , Humans , Structure-Activity Relationship , Molecular Structure , Gram-Negative Bacteria/drug effects , Klebsiella pneumoniae/drug effects , Gram-Positive Bacteria/drug effects , Cell Survival/drug effects , Dose-Response Relationship, Drug
12.
Diagn Microbiol Infect Dis ; 110(1): 116436, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39003931

ABSTRACT

Antimicrobial susceptibility testing (AST) from blood culture (BC) may take several days, limiting the eventual impact on antimicrobial stewardship. Hence, rapid AST systems represent a valuable support in shorting the time-to-response. In this work, the Quantamatrix dRASTTM system (dRAST) was evaluated for rapid AST on 100 monomicrobial BCs (50 Gram-negatives and 50 Gram-positives), including several isolates with clinically relevant resistance mechanisms. AST results were provided in 6-hours, on average. Compared to Micronaut (Merlin) system based on broth microdilution, dRAST exhibited an overall categorical agreement of 92.5 %, essential agreement of 89.0 %, and mean bias of 15.9 %. Category overestimation (potentially leading to unnecessary high-dosage treatment or to exclude active agents) and category underestimation (potentially leading to underdosing or using ineffective agents) were observed in 4.3 % and 3.1 % of cases, respectively. Even though several issues were reported, results confirmed the potential contribution of dRAST to shorten the BCs clinical microbiology workflow and management.


Subject(s)
Anti-Bacterial Agents , Blood Culture , Microbial Sensitivity Tests , Microbial Sensitivity Tests/methods , Humans , Blood Culture/methods , Anti-Bacterial Agents/pharmacology , Gram-Negative Bacteria/drug effects , Gram-Negative Bacteria/isolation & purification , Gram-Positive Bacteria/drug effects , Gram-Positive Bacteria/isolation & purification , Bacteria/drug effects , Bacteria/isolation & purification , Bacteria/classification , Bacteremia/microbiology , Time Factors
13.
Molecules ; 29(12)2024 Jun 16.
Article in English | MEDLINE | ID: mdl-38930924

ABSTRACT

A chemical and biological exploration of the European polypore Dentipellis fragilis afforded two previously undescribed natural products (1 and 2), together with three known derivatives (3-5). Chemical structures of the isolated compounds were confirmed through 1D/2D NMR spectroscopic analyses, mass spectrometry, and by comparison with the reported literature. The relative and absolute configurations of 1 were determined according to the ROESY spectrum and time-dependent density functional theory electronic circular dichroism (TDDFT-ECD), respectively. Furthermore, the absolute configuration of dentipellinol (3) was revisited and revealed to be of (R) configuration. All the isolated compounds were assessed for their cytotoxic and antimicrobial activities, with some being revealed to have weak to moderate antimicrobial activity, particularly against Gram-positive bacteria.


Subject(s)
Microbial Sensitivity Tests , Humans , Molecular Structure , Basidiomycota/chemistry , Magnetic Resonance Spectroscopy , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/isolation & purification , Circular Dichroism , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Anti-Infective Agents/isolation & purification , Gram-Positive Bacteria/drug effects , Cell Line, Tumor
14.
Dalton Trans ; 53(26): 10890-10900, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38874585

ABSTRACT

Herein, we describe the synthesis and characterisation of four new supramolecular cobalt conjugates of antimicrobial peptides functionalised with terpyridine ligands (L). Peptides were chosen based on the well-established arginine-tryptophan (RW)3 motif, with terpyridine-derivatized lysine (Lys(tpy)) added to the sequence, or replacing tryptophan residues. Self-assembly of the antimicrobial peptides with Co(BF4)2·6H2O formed exclusively CoL2 dimers (for peptides with one tpy ligand each) and Co2L4 metallo-macrocycles (for peptides with two tpy ligands for each peptide), which could be 'locked' by oxidation of Co(+II) to Co(+III) with ammonium ceric nitrate. The Co-peptide complexes were characterised by mass spectrometry and in solution by NMR spectroscopy, including 2D diffusion ordered NMR spectroscopy (DOSY) which confirmed the proposed stoichiometries. The antimicrobial activity of the novel peptides and their metallo-supramolecular assemblies was investigated by determination of their minimal inhibitory concentration (MIC) against a panel of Gram-positive and Gram-negative bacteria. Complexation with cobalt increases the activity of the peptides in almost every case. Most of the new metal-peptide conjugates showed good activity against Gram-positive bacteria, including a multi-resistant S. aureus strain and the opportunistic pathogenic yeast C. albicans (down to 7 µmol l-1 for the most active Co2L4 derivate), a value that is increased five-fold compared to the lysine-derivatized peptide ligand alone. Interestingly, conjugates of the CoL2 type also showed decent activity against Gram-negative bacteria including the WHO-flagged problematic A. baumannii strain (down to 18 µmol l-1 for the most active derivative).


Subject(s)
Anti-Bacterial Agents , Cobalt , Gram-Positive Bacteria , Microbial Sensitivity Tests , Cobalt/chemistry , Cobalt/pharmacology , Gram-Positive Bacteria/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Gram-Negative Bacteria/drug effects , Coordination Complexes/pharmacology , Coordination Complexes/chemistry , Coordination Complexes/chemical synthesis , Antimicrobial Peptides/chemistry , Antimicrobial Peptides/pharmacology , Antimicrobial Peptides/chemical synthesis , Ligands
15.
Nano Lett ; 24(26): 7868-7878, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38912706

ABSTRACT

Wound infections, especially those caused by pathogenic bacteria, present a considerable public health concern due to associated complications and poor therapeutic outcomes. Herein, we developed antibacterial nanoparticles, namely, PGTP, by coordinating guanidine derivatives with a porphyrin-based sonosensitizer. The synthesized PGTP nanoparticles, characterized by their strong positive charge, effectively disrupted the bacterial biosynthesis process through charge interference, demonstrating efficacy against both Gram-negative and Gram-positive bacteria. Additionally, PGTP nanoparticles generated reactive oxygen species under ultrasound stimulation, resulting in the disruption of biofilm integrity and efficient elimination of pathogens. RNA-seq analysis unveiled the detailed mechanism of wound healing, revealing that PGTP nanoparticles, when coupled with ultrasound, impair bacterial metabolism by interfering with the synthesis and transcription of amino acids. This study presents a novel approach to combatting wound infections through ultrasound-driven charge-interfering therapy, facilitated by advanced antibacterial nanomaterials.


Subject(s)
Anti-Bacterial Agents , Biofilms , Nanoparticles , Wound Infection , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/therapeutic use , Wound Infection/drug therapy , Wound Infection/microbiology , Nanoparticles/chemistry , Nanoparticles/therapeutic use , Biofilms/drug effects , Animals , Mice , Ultrasonic Waves , Reactive Oxygen Species/metabolism , Wound Healing/drug effects , Humans , Porphyrins/chemistry , Porphyrins/pharmacology , Porphyrins/therapeutic use , Ultrasonic Therapy/methods , Gram-Positive Bacteria/drug effects , Gram-Negative Bacteria/drug effects
16.
Bioorg Med Chem ; 109: 117810, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38906069

ABSTRACT

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


Subject(s)
Antifungal Agents , Aspergillus fumigatus , Candida albicans , Microbial Sensitivity Tests , Porphyrins , Porphyrins/pharmacology , Porphyrins/chemistry , Porphyrins/chemical synthesis , Aspergillus fumigatus/drug effects , Candida albicans/drug effects , Antifungal Agents/pharmacology , Antifungal Agents/chemical synthesis , Antifungal Agents/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Gram-Positive Bacteria/drug effects , Staphylococcus aureus/drug effects , Structure-Activity Relationship , Molecular Structure , Dose-Response Relationship, Drug , Fungi/drug effects
17.
Expert Opin Pharmacother ; 25(8): 1027-1037, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38863433

ABSTRACT

INTRODUCTION: Infections due to multidrug-resistant organisms (MDRO) are a serious concern for public health with high morbidity and mortality. Though many antibiotics have been introduced to manage these infections, there are remaining concerns regarding the optimal management of Gram-positive MDROs. AREAS COVERED: A literature search on the PubMed/Medline database was conducted. We applied no language and time limits for the search strategy. In this narrative review, we discuss the current options for managing Gram-positive MDROs as well as non-traditional antibacterial agents in development. EXPERT OPINION: Despite their introduction more than 70 years ago, glycopeptides are still the cornerstone in treating Gram-positive infections: all registrative studies of new antibiotics have glycopeptides as control; these studies are designed as not inferior studies, therefore it is almost impossible to give recommendations other than the use of glycopeptides in the treatment of Gram-positive infections. The best evidence on treatments different from glycopeptides comes from post-hoc analysis and meta-analysis. Non-traditional antibacterial agents are being studied to aid in short and effective antibiotic therapies. The use of non-traditional antibacterial agents is not restricted to replacing traditional antibacterial agents with alternative therapies; instead, they should be used in combination with antibiotic therapies.


Subject(s)
Anti-Bacterial Agents , Drug Resistance, Multiple, Bacterial , Glycopeptides , Gram-Positive Bacteria , Gram-Positive Bacterial Infections , Humans , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/pharmacology , Gram-Positive Bacterial Infections/drug therapy , Gram-Positive Bacterial Infections/microbiology , Glycopeptides/therapeutic use , Gram-Positive Bacteria/drug effects , Drug Development , Animals
18.
F1000Res ; 13: 36, 2024.
Article in English | MEDLINE | ID: mdl-38872735

ABSTRACT

Background: Tigecycline, a glycylcycline antibiotic is a promising option for the treatment of single or multidrug resistant pathogens. The aim of the study was to evaluate the in-vitro Tigecycline susceptibility of various pathogens from clinical samples received at the tertiary care hospitals in South India. Methods: The analysis of specimens from patients admitted were carried out in this prospective cross sectional study. The identification and antimicrobial susceptibility testing was performed by semi-automated Vitek 2 systems and Kirby Bauer method. Pattern of data analysis was done by descriptive statistics. Results: Among 2574 isolates, 812 isolates were Gram positive pathogens and 1762 isolates were Gram negative pathogens. Resistance to Tigecycline was more common among Gram negative pathogens (18.62%) in comparison to the Gram positive pathogens (0.49%). Among 740 Extended Spectrum Beta Lactamases (ESBL) producers such as Klebsiella species & E coli, 629 isolates were susceptible, and 93 isolates were resistant to the tigecycline. All the methicillin resistant Staphylococcus aureus (MRSA) isolates were susceptible to tigecycline. Conclusion: Multidrug resistant (MDR) pathogens like Acinetobacter species, and Klebsiella species were found to be highly effective in vitro to tigecycline for elimination of infections caused by both Gram positive and Gram negative pathogens. The use of combination therapy becomes crucial to prevent the development of Pan Drug resistance.


Subject(s)
Drug Resistance, Multiple, Bacterial , Microbial Sensitivity Tests , Tertiary Care Centers , Tigecycline , Tigecycline/pharmacology , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Cross-Sectional Studies , Minocycline/analogs & derivatives , Minocycline/pharmacology , Minocycline/therapeutic use , Gram-Negative Bacteria/drug effects , Prospective Studies , India , Gram-Positive Bacteria/drug effects
19.
Eur J Med Chem ; 274: 116544, 2024 Aug 05.
Article in English | MEDLINE | ID: mdl-38850855

ABSTRACT

Antibiotic resistance is becoming increasingly severe. The development of small molecular antimicrobial peptides is regarded as a promising design strategy for antibiotics. Here, a series of bisphenol derivatives with amphiphilic structures were designed and synthesized as antibacterial agents by imitating the design strategy of antimicrobial peptides. After a series of structural optimizations, lead compound 43 was identified, which exhibited excellent antibacterial activity against Gram-positive bacterial strains (MICs = 0.78-1.56 µg/mL), poor hemolytic activity (HC50 > 200 µg/mL), and low cytotoxicity (CC50 > 100 µg/mL). Further biological evaluation results indicated that 43 exerted antibacterial effects by directly destroying bacterial cell membranes and displayed rapid bactericidal properties (within 0.5-1 h), leading to a very low probability of drug resistance. Moreover, in a murine model of corneal infection, 43 exhibited a strong in vivo antibacterial efficacy. These findings indicate that 43 is a promising candidate compound for the treatment of bacterial infections.


Subject(s)
Anti-Bacterial Agents , Benzhydryl Compounds , Gram-Positive Bacteria , Microbial Sensitivity Tests , Phenols , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Phenols/pharmacology , Phenols/chemistry , Phenols/chemical synthesis , Animals , Gram-Positive Bacteria/drug effects , Mice , Structure-Activity Relationship , Benzhydryl Compounds/pharmacology , Benzhydryl Compounds/chemistry , Benzhydryl Compounds/chemical synthesis , Molecular Structure , Cell Membrane/drug effects , Dose-Response Relationship, Drug , Humans , Hemolysis/drug effects , Drug Development
20.
Vet Med Sci ; 10(4): e1498, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38896065

ABSTRACT

BACKGROUND: Bersama abyssinica Fresen is a plant that is used in folk medicine for the treatment of mastitis and other infectious diseases. OBIECTIVE: The antibacterial activity of methanol crude extract of plant was evaluated against three common bacterial pathogens, including Gram positive (Staphylococcus aureus) and Gram negative (Escherichia coli and Pseudomonas aeruginosa). METHODS: The antibacterial activities and minimum inhibitory concentration of B. abyssinica crude extracts were evaluated using agar-well diffusion and broth dilution methods according to the National Committee for Clinical Laboratory Standards (NCCLS). RESULTS: A significant difference in the antibacterial activity of crude extracts was observed among different levels of concentration against tested isolates. A higher mean inhibition zone diameter was recorded in E. coli (29.2 ± 1.5 mm), followed by S. aureus (27.8 ± 1.1 mm) and P. aeruginosa (18.0 ± 0.7 mm) at a concentration of 100 mg/mL. The antibacterial activity of crude plant extract at 100 mg/mL was comparable with that of a standard antibiotic (27.6 ± 2.6) against S. aureus and E. coli isolates. The findings indicated that bacterial growth inhibition increased as the concentration of the crude extracts increased. E. coli and S. aureus isolates showed significantly higher susceptibilities to crude extracts than P. aeruginosa at all concentrations. The minimum inhibitory concentrations of extracts against S. aureus, E. coli and P. aeruginosa isolates were 0.78 mg/mL, 1.56 mg/mL and 1.56 mg/mL, respectively. CONCLUSIONS: All tested pathogenic bacterial species were susceptible to plant leaf extract and broad-spectrum activity against Gram-positive and Gram-negative bacteria. The study recommends further fractionation of the B. abyssinica plant that contributes to its antibacterial activity and understands the mode of action of this plant against bacteria and other microbes.


Subject(s)
Anti-Bacterial Agents , Gram-Negative Bacteria , Microbial Sensitivity Tests , Plant Extracts , Plant Extracts/pharmacology , Plant Extracts/chemistry , Anti-Bacterial Agents/pharmacology , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Escherichia coli/drug effects , Staphylococcus aureus/drug effects , Pseudomonas aeruginosa/drug effects
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