Antimicrobial Resistance Profile of Planktonic and Biofilm Cells of Staphylococcus aureus and Coagulase-Negative Staphylococci

The objective of the present study was to determine the antimicrobial resistance profile of planktonic and biofilm cells of Staphylococcus aureus and coagulase-negative staphylococci (CoNS). Two hundred Staphylococcus spp. strains were studied, including 50 S. aureus and 150 CoNS strains (50 S. epidermidis, 20 S. haemolyticus, 20 S. warneri, 20 S. hominis, 20 S. lugdunensis, and 20 S. saprophyticus). Biofilm formation was investigated by adherence to polystyrene plates. Positive strains were submitted to the broth microdilution method to determine the minimum inhibitory concentration (MIC) for planktonic and biofilm cells and the minimal bactericidal concentration for biofilm cells (MBCB). Forty-nine Staphylococcus spp. strains (14 S. aureus, 13 S. epidermidis, 13 S. saprophyticus, 3 S. haemolyticus, 1 S. hominis, 3 S. warneri, and 2 S. lugdunensis) were biofilm producers. These isolates were evaluated regarding their resistance profile. Determination of planktonic cell MIC identified three (21.4%) S. aureus strains that were resistant to oxacillin and six (42.8%) that were resistant to erythromycin. Among the CoNS, 31 (88.6%) strains were resistant to oxacillin, 14 (40%) to erythromycin, 18 (51.4%) to gentamicin, and 8 (22.8%) to sulfamethoxazole/trimethoprim. None of the planktonic isolates were resistant to vancomycin or linezolid. MICs were 2-, 4-, 8-, and up to 16-fold higher for biofilm cells than for planktonic cells. This observation was more common for vancomycin and erythromycin. The MBCB ranged from 8 to >256 µg/mL for oxacillin, 128 to >128 µg/mL for vancomycin, 256 to >256 µg/mL for erythromycin and gentamicin, >64 µg/mL for linezolid, and 32/608 to >32/608 µg/mL for sulfamethoxazole/trimethoprim. The results showed considerably higher MICs for S. aureus and CoNS biofilm cells compared to planktonic cells. Analysis of MBCM confirmed that even high concentrations of vancomycin were unable to eliminate the biofilms of S. aureus and CoNS species. Linezolid was the most effective drug in inhibiting staphylococci in the biofilm, without an increase in the MIC, when compared to planktonic cells. None of the isolates were resistant to this drug.     

Synthesis,Biological Activity and Molecular Docking Studies of Novel Nicotinic Acid Derivatives

In our research, we used nicotinic acid as a starting compound, which was subjected to a series of condensation reactions with appropriate aldehydes. As a result of these reactions, we were able to obtain a series of twelve acylhydrazones, two of which showed promising activity against Gram-positive bacteria (MIC = 1.95–15.62 µg/mL), especially against Staphylococcus epidermidis ATCC 12228 (MIC = 1.95 µg/mL). Moreover, the activity of compound 13 against the Staphylococcus aureus ATCC 43300 strain, i.e., the MRSA strain, was MIC = 7.81 µg/mL. Then, we subjected the entire series of acylhydrazones to a cyclization reaction in the acetic anhydride, thanks to which we were able to obtain twelve new 3-acetyl-2,5-disubstituted-1,3,4-oxadiazoline derivatives. Obtained 1,3,4-oxadiazolines were also tested for antimicrobial activity. The results showed high activity of compound 25 with a 5-nitrofuran substituent, which was active against all tested strains. The most promising activity of this compound was found against Gram-positive bacteria, in particular against Bacillus subtilis ATCC 6633 and Staphylococcus aureus ATCC 6538 (MIC = 7.81 µg/mL) and ATCC 43300 MRSA strains (MIC = 15.62 µg/mL). Importantly, the best performing compounds did not show cytotoxicity against normal cell lines. It seems practical to use some of these compounds or their derivatives in the future in the prevention and treatment of infections caused by some pathogenic or opportunistic microorganisms.     

Silver Nanoparticles from Oregano Leaves’ Extracts as Antimicrobial Components for Non-Infected Hydrogel Contact Lenses

The oregano leaves’ extract (ORLE) was used for the formation of silver nanoparticles (AgNPs(ORLE)). ORLE and AgNPs(ORLE) (2 mg/mL) were dispersed in polymer hydrogels to give the pHEMA@ORLE_2 and pHEMA@AgNPs(ORLE)_2 using hydroxyethyl–methacrylate (HEMA). The materials were characterized by X-ray fluorescence (XRF) spectroscopy, X-ray powder diffraction analysis (XRPD), thermogravimetric differential thermal analysis (TG-DTA), derivative thermogravimetry/differential scanning calorimetry (DTG/DSC), ultraviolet (UV-Vis), and attenuated total reflection mode (ATR-FTIR) spectroscopies in solid state and UV–Vis in solution. The crystallite size value, analyzed with XRPD, was determined at 20 nm. The antimicrobial activity of the materials was investigated against Gram-negative bacterial strains Pseudomonas aeruginosa (P. aeruginosa) and Escherichia coli (E. coli). The Gram-positive ones of the genus of Staphylococcus epidermidis (S. epidermidis) and Staphylococcus aureus (S. aureus) are known to be involved in microbial keratitis by the means of inhibitory zone (IZ), minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC). The IZs, which developed upon incubation of P. aeruginosa, E. coli, S. epidermidis, and S. aureus with paper discs soaked in 2 mg/mL of AgNPs(ORLE), were 11.7 ± 0.7, 13.5 ± 1.9, 12.7 ± 1.7, and 14.3 ± 1.7 mm. When the same dose of ORLE was administrated, the IZs were 10.2 ± 0.7, 9.2 ± 0.5, 9.0 ± 0.0, and 9.0 ± 0.0 mm. The percent of bacterial viability when they were incubated over the polymeric hydrogel discs of pHEMA@AgNPs(ORLE)_2 was interestingly low (66.5, 88.3, 77.7, and 59.6%, respectively, against of P. aeruginosa, E. coli, S. epidermidis, and S. aureus) and those of pHEMA@ORLE_2 were 89.3, 88.1, 92.8, and 84.6%, respectively. Consequently, pHEMA@AgNPs(ORLE)_2 could be an efficient candidate toward the development of non-infectious contact lenses.     

Rapid Bioassay-Guided Isolation of Antibacterial Clerodane Type Diterpenoid from Dodonaea viscosa (L.) Jaeq.

Plant extracts are complex matrices and, although crude extracts are widely in use, purified compounds are pivotal in drug discovery. This study describes the application of automated preparative-HPLC combined with a rapid off-line bacterial bioassay, using reduction of a tetrazolium salt as an indicator of bacterial metabolism. This approach enabled the identification of fractions from Dodonaea viscosa that were active against Staphylococcus aureus and Escherichia coli, which, ultimately, resulted in the identification of a clerodane type diterpenoid, 6β-hydroxy-15,16-epoxy-5β, 8β, 9β, 10α-cleroda-3, 13(16), 14-trien-18-oic acid, showing bacteriostatic activity (minimum inhibitory concentration (MIC) = 64–128 µg/mL) against test bacteria. To the best of our knowledge, this is the first report on antibacterial activity of this metabolite from D. viscosa.     

Synthesis and Evaluation of Novel Oxyalkylated Derivatives of 2′,4′-Dihydroxychalcone as Anti-Oomycete Agents against Bronopol Resistant Strains of Saprolegnia sp.

A series of novel oxyalkylchalcones substituted with alkyl groups were designed and synthesized, and the antioomycete activity of the series was evaluated in vitro against Saprolegnia strains. All tested O-alkylchalcones were synthesized by means of nucleophilic substitution from the natural compound 2′,4′-dihydroxychalcone (1) and the respective alkyl bromide. The natural chalcone (1) and 10 synthetic oxyalkylchalcones (2–11) were tested against Saprolegnia parasitica and Saprolegnia australis. Among synthetic analogs, 2-hydroxy,4-farnesyloxychalcone (11) showed the most potent activity against Saprolegnia sp., with MIC and MOC values of 125 µg/mL (similar to bronopol at 150 µg/mL) and 175 µg/mL, respectively; however, 2′,4′-dihydroxychalcone (1) was the strongest and most active molecule, with MIC and MOC values of 6.25 µg/mL and 12.5 µg/mL.     

New Coumarins and Anti-Inflammatory Constituents from the Fruits of Cnidium monnieri

The fruit of Cnidium monnieri is commercially used as healthcare products for the improvement of impotence and skin diseases. Three new coumarins, 3''-O-methylmurraol (1), rel-(1''S,2''S)-1''-O-methylphlojodicarpin (2), and (1''S,2''S)-1''-O-methylvaginol (3), have been isolated from the fruits of C. monnieri, together with 14 known compounds (4–17). The structures of these new compounds were determined through spectroscopic and MS analyses. Compounds 1, 4–12, and 14–17 exhibited inhibition (IC₅₀ ≤ 7.31 µg/mL) of superoxide anion generation by human neutrophils in response to formyl-l-methionyl-l-leucyl-l-phenylalanine/cytochalasin B (fMLP/CB). Compounds 7, 9–11, 15, and 17 inhibited fMLP/CB-induced elastase release with IC₅₀ values ≤7.83 µg/mL. This investigation reveals that bioactive isolates (especially 6, 7, 14, and 17) could be further developed as potential candidates for the treatment or prevention of various inflammatory diseases.     

Pereskia aculeata Muller (Cactaceae) Leaves: Chemical Composition and Biological Activities

The aims of this work were to study the chemical composition of the essential oil from the leaves of Pereskia aculeata and to evaluate some biological activities of three leaf extracts. The phenolic content, antioxidant activity, and in vitro antimicrobial and antifungal activities were determined. The methanol extract showed antioxidant activity (EC₅₀ 7.09 mg/mL) and high polyphenols content (15.04 ± 0.31 mg gallic acid equivalents (GAE)/g). The petroleum ether extract exhibited potent antibacterial activity against Escherichia coli, whereas the chloroform extract showed inhibitory activity against Bacillus cereus and Staphylococcus aureus. The petroleum ether and methanol extracts were more effective in inhibiting the growth of Aspergillus versicolor. The possible cytotoxicity of extracts on neuroblastoma SH-SY5Y cancer cell line and the influence on adenylate cyclase (ADCY) expression was also studied. P. aculeata chloroform extract showed antiproliferative activity with an IC₅₀ value of 262.83 µg/mL. Treatments of SH-SY5Y neuroblastoma cells with 100 µg/mL of methanol extract significantly reduced ADCY1 expression.     

Antibacterial Activity of New Oxazolidin-2-One Analogues in Methicillin-Resistant Staphylococcus aureus Strains

Staphylococcus aureus is one of the most common causes of nosocomial infections. The purpose of this study was the synthesis and in vitro evaluation of antimicrobial activity of 10 new 3-oxazolidin-2-one analogues on 12 methicillin resistant S. aureus (MRSA) clinical isolates. S. aureus confirmation was achieved via catalase and coagulase test. Molecular characterization of MRSA was performed by amplification of the mecA gene. Antimicrobial susceptibility was evaluated via the Kirby-Bauer disc diffusion susceptibility test protocol, using commonly applied antibiotics and the oxazolidinone analogues. Only (R)-5-((S)-1-dibenzylaminoethyl)-1,3-oxazolidin-2-one (7a) exhibited antibacterial activity at 6.6 μg. These results, allow us to infer that molecules such as 7a can be potentially used to treat infections caused by MRSA strains.     

Bioactive Chemical Constituents from the Brown Alga Homoeostrichus formosana

A new chromene derivative, 2-(4'',8''-dimethylnona-3''E,7''-dienyl)-8-hydroxy-2,6-dimethyl-2H-chromene (1) together with four known natural products, methylfarnesylquinone (2), isololiolide (3), pheophytin a (4), and β-carotene (5) were isolated from the brown alga Homoeostrichus formosana. The structure of 1 was determined by extensive 1D and 2D spectroscopic analyses. Acetylation of 1 yielded the monoacetylated derivative 2-(4'',8''-dimethylnona-3''E,7''-dienyl)-8-acetyl-2,6-dimethyl-2H-chromene (6). Compounds 1–6 exhibited various levels of cytotoxic, antibacterial, and anti-inflammatory activities. Compound 2 was found to display potent in vitro anti-inflammatory activity by inhibiting the generation of superoxide anion (IC₅₀ 0.22 ± 0.03 μg/mL) and elastase release (IC₅₀ 0.48 ± 0.11 μg/mL) in FMLP/CB-induced human neutrophils.     

Novel N-Substituted 3-Aryl-4-(diethoxyphosphoryl)azetidin-2-ones as Antibiotic Enhancers and Antiviral Agents in Search for a Successful Treatment of Complex Infections

A novel series of N-substituted cis- and trans-3-aryl-4-(diethoxyphosphoryl)azetidin-2-ones were synthesized by the Kinugasa reaction of N-methyl- or N-benzyl-(diethyoxyphosphoryl)nitrone and selected aryl alkynes. Stereochemistry of diastereoisomeric adducts was established based on vicinal H3–H4 coupling constants in azetidin-2-one ring. All the obtained azetidin-2-ones were evaluated for the antiviral activity against a broad range of DNA and RNA viruses. Azetidin-2-one trans-11f showed moderate inhibitory activity against human coronavirus (229E) with EC₅₀ = 45 µM. The other isomer cis-11f was active against influenza A virus H1N1 subtype (EC₅₀ = 12 µM by visual CPE score; EC₅₀ = 8.3 µM by TMS score; MCC > 100 µM, CC₅₀ = 39.9 µM). Several azetidin-2-ones 10 and 11 were tested for their cytostatic activity toward nine cancerous cell lines and several of them appeared slightly active for Capan-1, Hap1 and HCT-116 cells values of IC₅₀ in the range 14.5–97.9 µM. Compound trans-11f was identified as adjuvant of oxacillin with significant ability to enhance the efficacy of this antibiotic toward the highly resistant S. aureus strain HEMSA 5. Docking and molecular dynamics simulations showed that enantiomer (3R,4S)-11f can be responsible for the promising activity due to the potency in displacing oxacillin at β-lactamase, thus protecting the antibiotic from undesirable biotransformation.     

New 14-Membered Cyclopeptide Alkaloids from Zizyphus oxyphylla Edgew

Two new 14-membered cyclopeptide alkaloids, Oxyphylline B (4) and Oxyphylline C (5), along with three known 13-membered cyclopeptide alkaloids, were isolated from stem and roots of Zizyphus oxyphylla Edgew. The compounds were tested for antibacterial activity. Oxyphylline B (4) showed comparatively better antibacterial activities against Escherichia coli (MIC, 5 μg/mL) than other compounds. This compound also exhibited weak antimicrobial activities against Staphylococcus aureus (MIC, 25 μg/mL), Pseudomonas aeruginosa (MIC, 50 μg/mL) and Salmonella typhi (MIC, 50 μg/mL).     

Synthesis,Biological Evaluation and 2D-QSAR Study of Halophenyl Bis-Hydrazones as Antimicrobial and Antitubercular Agents

In continuation of our endeavor towards the development of potent and effective antimicrobial agents, three series of halophenyl bis-hydrazones (14a–n, 16a–d, 17a and 17b) were synthesized and evaluated for their potential antibacterial, antifungal and antimycobacterial activities. These efforts led to the identification of five molecules 14c, 14g, 16b, 17a and 17b (MIC range from 0.12 to 7.81 μg/mL) with broad antimicrobial activity against Mycobacterium tuberculosis; Aspergillus fumigates; Gram positive bacteria, Staphylococcus aureus, Streptococcus pneumonia, and Bacillis subtilis; and Gram negative bacteria, Salmonella typhimurium, Klebsiella pneumonia, and Escherichia coli. Three of the most active compounds, 16b, 17a and 17b, were also devoid of apparent cytotoxicity to lung cancer cell line A549. Amphotericin B and ciprofloxacin were used as references for antifungal and antibacterial screening, while isoniazid and pyrazinamide were used as references for antimycobacterial activity. Furthermore, three Quantitative Structure Activity Relationship (QSAR) models were built to explore the structural requirements controlling the different activities of the prepared bis-hydrazones.     

Polyphenylglyoxamide-Based Amphiphilic Small Molecular Peptidomimetics as Antibacterial Agents with Anti-Biofilm Activity

The rapid emergence of drug-resistant bacteria is a major global health concern. Antimicrobial peptides (AMPs) and peptidomimetics have arisen as a new class of antibacterial agents in recent years in an attempt to overcome antibiotic resistance. A library of phenylglyoxamide-based small molecular peptidomimetics was synthesised by incorporating an N-alkylsulfonyl hydrophobic group with varying alkyl chain lengths and a hydrophilic cationic group into a glyoxamide core appended to phenyl ring systems. The quaternary ammonium iodide salts 16d and 17c showed excellent minimum inhibitory concentration (MIC) of 4 and 8 μM (2.9 and 5.6 μg/mL) against Staphylococcus aureus, respectively, while the guanidinium hydrochloride salt 34a showed an MIC of 16 μM (8.5 μg/mL) against Escherichia coli. Additionally, the quaternary ammonium iodide salt 17c inhibited 70% S. aureus biofilm formation at 16 μM. It also disrupted 44% of pre-established S. aureus biofilms at 32 μM and 28% of pre-established E. coli biofilms 64 μM, respectively. A cytoplasmic membrane permeability study indicated that the synthesised peptidomimetics acted via disruption and depolarisation of membranes. Moreover, the quaternary ammonium iodide salts 16d and 17c were non-toxic against human cells at their therapeutic dosages against S. aureus.     

Design,Synthesis, Antibacterial,Antifungal and Anticancer Evaluations of Novel β-Pinene Quaternary Ammonium Salts

β-pinene is a monoterpene isolated from turpentine oil and numerous other plants’ essential oils, which has a broad spectrum of biological activities. In the current work, six novel β-pinene quaternary ammonium (β-PQA) salts were synthesized and evaluated in vitro for their antifungal, antibacterial and anticancer activities. The in vitro assay results revealed that compounds 4a and 4b presented remarkable antimicrobial activity against the tested fungi and bacteria. In particular, compound 4a showed excellent activities against F. oxysporum f.sp. niveum, P. nicotianae var.nicotianae, R. solani, D. pinea and Fusicoccumaesculi, with EC₅₀ values of 4.50, 10.92, 9.45, 10.82 and 6.34 μg/mL, respectively. Moreover, compound 4a showed the best antibacterial action against E. coli, P. aeruginosa, S. aureus and B. subtilis, with MIC at 2.5, 0.625, 1.25 and 1.25 μg/mL, respectively. The anticancer activity results demonstrated that compounds 4a, 4b, 4c and 4f exhibited remarkable activity against HCT-116 and MCF-7 cell lines, with IC₅₀ values ranged from 1.10 to 25.54 μM. Notably, the compound 4c displayed the strongest cytotoxicity against HCT-116 and MCF-7 cell lines, with the IC₅₀ values of 1.10 and 2.46 μM, respectively. Furthermore, preliminary antimicrobial mechanistic studies revealed that compound 4a might cause mycelium abnormalities of microbial, cell membrane permeability changes and inhibition of the activity of ATP. Altogether, these findings open interesting perspectives to the application of β-PQA salts as a novel leading structure for the development of effective antimicrobial and anticancer agents.     

Peptide/β-Peptoid Hybrids with Activity against Vancomycin-Resistant Enterococci: Influence of Hydrophobicity and Structural Features on Antibacterial and Hemolytic Properties

Infections with enterococci are challenging to treat due to intrinsic resistance to several antibiotics. Especially vancomycin-resistant Enterococcus faecium and Enterococcus faecalis are of considerable concern with a limited number of efficacious therapeutics available. From an initial screening of 20 peptidomimetics, 11 stable peptide/β-peptoid hybrids were found to have antibacterial activity against eight E. faecium and E. faecalis isolates. Microbiological characterization comprised determination of minimal inhibitory concentrations (MICs), probing of synergy with antibiotics in a checkerboard assay, time–kill studies, as well as assessment of membrane integrity. E. faecium isolates proved more susceptible than E. faecalis isolates, and no differences in susceptibility between the vancomycin-resistant (VRE) and -susceptible E. faecium isolates were observed. A test of three peptidomimetics (Ac-[hArg-βNsce]₆-NH₂, Ac-[hArg-βNsce-Lys-βNspe]₃-NH₂ and Oct-[Lys-βNspe]₆-NH₂) in combination with conventional antibiotics (vancomycin, gentamicin, ciprofloxacin, linezolid, rifampicin or azithromycin) revealed no synergy. The same three potent analogues were found to have a bactericidal effect with a membrane-disruptive mode of action. Peptidomimetics Ac-[hArg-βNsce-Lys-βNspe]₃-NH₂ and Oct-[Lys-βNspe]₆-NH₂ with low MIC values (in the ranges 2–8 µg/mL and 4–16 µg/mL against E. faecium and E. faecalis, respectively) and displaying weak cytotoxic properties (i.e., <10% hemolysis at a ~100-fold higher concentration than their MICs; IC₅₀ values of 73 and 41 µg/mL, respectively, against HepG2 cells) were identified as promising starting points for further optimization studies.     

New Labdane-Type Diterpenoids and Anti-Inflammatory Constituents from Hedychium coronarium

Four new labdane-type diterpenoids: hedychicoronarin (1), peroxycoronarin D (2), 7β-hydroxycalcaratarin A (3), and (E)-7β-hydroxy-6-oxo-labda-8(17),12-diene-15,16-dial (4), have been isolated from the rhizomes of Hedychium coronarium, together with 13 known compounds (5–17). The structures of these new compounds were determined through spectroscopic and MS analyses. Compounds 3, 5, 6, and 10 exhibited inhibition (IC₅₀ values ≤4.52 μg/mL) of superoxide anion generation by human neutrophils in response to formyl-L-methionyl-L-leucyl-L-phenylalanine/cytochalasin B (fMLP/CB). Compounds 3–6, 10, and 11 inhibited fMLP/CB-induced elastase release with IC₅₀ values ≤6.17 μg/mL.     

Identification of Bioactivity,Volatile and Fatty Acid Profile in Supercritical Fluid Extracts of Mexican arnica

Supercritical fluid extraction (SFE) is a sustainable technique used for the extraction of lipophilic metabolites such as pigments and fatty acids. Arnica plant is considered a potential candidate material with high antioxidant and antimicrobial activities. Therefore, in this study, a locally available Heterotheca inuloides, also known as Mexican arnica, was analyzed for the extraction of high-value compounds. Based on different pressure (P), temperature (T), and co-solvent (CoS), four treatments (T) were prepared. A maximum 7.13% yield was recovered from T2 (T = 60 °C, P = 10 MPa, CoS = 8 g/min), followed by 6.69% from T4 (T = 60 °C, P = 30 MPa, CoS = 4 g/min). Some bioactive sesquiterpenoids such as 7-hydroxycadalene, caryophyllene and δ-cadinene were identified in the extracts by GC/MS. The fatty acid profile revealed that the main components were palmitic acid (C16:0), followed by linoleic acid (C18:2ω6c), α-linolenic acid (C18:3ω3) and stearic acid (C18:0) differing in percent yield per treatment. Antibacterial activities were determined by the agar diffusion method, indicating that all the treatments exerted strong antibacterial activity against S. aureus, C. albicans, and E. coli strains. The antioxidant capacity of the extracts was also measured by three in vitro assays, DPPH, TEAC and FRAP, using Trolox as a standard. Results showed high antioxidant capacity enabling pharmaceutical applications of Mexican arnica.     

Influence of Ce3+ Substitution on Antimicrobial and Antibiofilm Properties of ZnCexFe2−xO4 Nanoparticles (X = 0.0, 0.02, 0.04, 0.06, and 0.08) Conjugated with Ebselen and Its Role Subsidised with γ-Radiation in Mitigating Human TNBC and Colorectal Adenocarcinoma Proliferation In Vitro

Cancers are a major challenge to health worldwide. Spinel ferrites have attracted attention due to their broad theranostic applications. This study aimed at investigating the antimicrobial, antibiofilm, and anticancer activities of ebselen (Eb) and cerium-nanoparticles (Ce-NPs) in the form of ZnCe_xFe_2−XO₄ on human breast and colon cancer cell lines. Bioassays of the cytotoxic concentrations of Eb and ZnCe_xFe_2−XO₄, oxidative stress and inflammatory milieu, autophagy, apoptosis, related signalling effectors, the distribution of cells through the cell-cycle phases, and the percentage of cells with apoptosis were evaluated in cancer cell lines. Additionally, the antimicrobial and antibiofilm potential have been investigated against different pathogenic microbes. The ZOI, and MIC results indicated that ZnCe_xFe_2−XO₄; X = 0.06 specimen reduced the activity of a wide range of bacteria and unicellular fungi at low concentration including P. aeruginosa (9.5 mm; 6.250 µg/mL), S. aureus (13.2 mm; 0.390 µg/mL), and Candida albicans (13.5 mm; 0.195 µg/mL). Reaction mechanism determination indicated that after ZnCe_xFe_2−xO₄; X = 0.06 treatment, morphological differences in S. aureus were apparent with complete lysis of bacterial cells, a concomitant decrease in the viable number, and the growth of biofilm was inhibited. The combination of Eb with ZFO or ZnCe_xFe_2−XO₄ with γ-radiation exposure showed marked anti-proliferative efficacy in both cell lines, through modulating the oxidant/antioxidant machinery imbalance, restoring the fine-tuning of redox status, and promoting an anti-inflammatory milieu to prevent cancer progression, which may be a valuable therapeutic approach to cancer therapy and as a promising antimicrobial agent to reduce the pathogenic potential of the invading microbes.     

Peptide/β-Peptoid Hybrids with Ultrashort PEG-Like Moieties: Effects on Hydrophobicity,Antibacterial Activity and Hemolytic Properties

PEGylation of antimicrobial peptides as a shielding tool that increases stability toward proteolytic degradation typically leads to concomitant loss of activity, whereas incorporation of ultrashort PEG-like amino acids (sPEGs) remains essentially unexplored. Here, modification of a peptide/β-peptoid hybrid with sPEGs was examined with respect to influence on hydrophobicity, antibacterial activity and effect on viability of mammalian cells for a set of 18 oligomers. Intriguingly, the degree of sPEG modification did not significantly affect hydrophobicity as measured by retention in reverse-phase HPLC. Antibacterial activity against both wild-type and drug-resistant strains of Escherichia coli and Acinetobacter baumannii (both Gram-negative pathogens) was retained or slightly improved (MICs in the range 2–16 µg/mL equal to 0.7–5.2 µM). All compounds in the series exhibited less than 10% hemolysis at 400 µg/mL. While the number of sPEG moieties appeared not to be clearly correlated with hemolytic activity, a trend toward slightly increased hemolytic activity was observed for analogues displaying the longest sPEGs. In contrast, within a subseries the viability of HepG2 liver cells was least affected by analogues displaying the longer sPEGs (with IC₅₀ values of ~1280 µg/mL) as compared to most other analogues and the parent peptidomimetic (IC₅₀ values in the range 330–800 µg/mL).     

Staphylococcus aureus and MRSA Growth and Biofilm Formation after Treatment with Antibiotics and SeNPs

Methicillin-resistant Staphylococcus aureus (MRSA) is a dangerous pathogen resistant to β-lactam antibiotics. Due to its resistance, it is difficult to manage the infections caused by this strain. We examined this issue in terms of observation of the growth properties and ability to form biofilms in sensitive S. aureus and MRSA after the application of antibiotics (ATBs)—ampicillin, oxacillin and penicillin—and complexes of selenium nanoparticles (SeNPs) with these ATBs. The results suggest the strong inhibition effect of SeNPs in complexes with conventional ATBs. Using the impedance method, a higher disruption of biofilms was observed after the application of ATB complexes with SeNPs compared to the group exposed to ATBs without SeNPs. The biofilm formation was intensely inhibited (up to 99% ± 7% for S. aureus and up to 94% ± 4% for MRSA) after application of SeNPs in comparison with bacteria without antibacterial compounds whereas ATBs without SeNPs inhibited S. aureus up to 79% ± 5% and MRSA up to 16% ± 2% only. The obtained results provide a basis for the use of SeNPs as a tool for the treatment of bacterial infections, which can be complicated because of increasing resistance of bacteria to conventional ATB drugs.