Antimicrobial resistance is a global threat, leading to an alarming increase in the prevalence of bacterial infections that can no longer be treated with available antibiotics. The World Health ...Organization estimates that by 2050 up to 10 million deaths per year could be associated with antimicrobial resistance, which would equal the annual number of cancer deaths worldwide. To overcome this emerging crisis, novel anti-bacterial compounds are urgently needed. There are two possible approaches in the fight against bacterial infections: a) targeting structures within bacterial cells, similar to existing antibiotics; and/or b) targeting virulence factors rather than bacterial growth. Here, for the first time, we provide a comprehensive overview of the key steps in the evaluation of potential new anti-bacterial and/or anti-virulence compounds. The methods described in this review include: a)
methods for the evaluation of novel compounds; b) anti-bacterial assays (MIC, MBC, Time-kill); b) anti-virulence assays (anti-biofilm, anti-quorum sensing, anti-adhesion); and c) evaluation of safety aspects (cytotoxicity assay and Ames test). Overall, we provide a detailed description of the methods that are an essential tool for chemists, computational chemists, microbiologists, and toxicologists in the evaluation of potential novel antimicrobial compounds. These methods are cost-effective and have high predictive value. They are widely used in preclinical studies to identify new molecular candidates, for further investigation in animal and human trials.
Aims
To investigate the synergistic activity of colistin and selenium nanoparticles (SeNPs) against pandrug‐resistant (PDR) Ac. baumannii.
Methods and Results
Chequerboard and time‐kill assays were ...employed to explore the potential synergistic interactions between colistin and SeNPs against Ac. baumannii isolates (8), previously determined as colistin‐resistant (MIC range 16–256 μg ml−1). Also, whole‐genome sequencing (WGS) and gene expression analyses were used to elucidate the mechanisms of colistin resistance. Exceptionally strong synergistic activity (FICI range 0.004–0.035) of colistin and SeNPs against colistin‐resistant isolates was revealed. Colistin (0.5 or 1 μg ml−1) used in combination with SeNPs (0.5 μg ml−1) was able to reduce initial inoculum during the first 4 h of incubation, in contrast to colistin (0.5, 1 or 2 μg ml−1) alone.
Conclusions
These findings propose colistin/SeNPs combination as a new option to fight PDR Ac. baumannii, the therapeutic possibilities of which should be proved in future in vivo studies.
Significance and Impact of Study
Here we present the first evidence of synergy between colistin and selenium compounds against bacteria in general. Also, WGS and gene expression analyses provide some new insights into Ac. baumannii colistin resistance mechanisms.
As we witness a global change occurring with the advent of e-scooters (electric scooters), it is clear that adequate measures need to be taken for the implementation of this means of transport. ...Bearing in mind that the user should be the focus of the proposed measures, the aim of this paper encompasses the analysis of e-scooter users’ travel patterns, as well as standard scooter users’ willingness to switch to e-scooters for different hypothetical scenarios, and the determination of factors that have an influence on the users’ willingness to switch. The scenarios include the availability of various infrastructure capacities for the city of Belgrade, namely, a separate infrastructure for e-scooters, or sharing the existing infrastructure with cyclists, pedestrians and motor vehicles. Standard methods of descriptive statistics, the McNemar–Bowker test of paired samples, and multinomial logistic regression were used in this paper. The results showed that there was a statistically significant difference in users’ willingness to use an e-scooter, depending on the available infrastructure. The results of multinomial logistic regression showed that the mode of transport used before and during the COVID-19 pandemic, as well as the average distance traveled, had a statistically significant impact on the users’ willingness to switch to e-scooters if they were allowed to use the cycling infrastructure. This paper also identifies additional factors that have a positive (environmental benefits, congestion avoidance) and negative (safety issues, lack of infrastructure, etc.) impact on users’ willingness to switch, which can be of use to decision-makers as a basic guideline for the adequate implementation of e-scooters in transport systems.
Biofilm production facilitates microbial colonization of wounds and catheters. Acinetobacter baumannii produces high levels of biofilm and causes difficult-to-treat nosocomial infections. Candida ...albicans is another strong biofilm producer which may facilitate A. baumannii adhesion by providing hyphae-mediated OmpA-binding sites. Here we tested the potential of 2′-hydroxychalcones to inhibit dual-species biofilm production of A. baumannii and Candida spp., and further predicted the mechanism of structure-related difference in activity. The results suggest that 2′-hydroxychalcones exhibit potent activity against Candida spp./A. baumannii dual-species biofilm production. Particularly active was trifluoromethyl-substituted derivative (p-CF
3
), which decreased C. albicans/A. baumannii biomass produced on vein-indwelling parts of the central venous catheterization set by up to 99%. Further, higher OmpA-binding affinity was also calculated for p-CF
3
, which together with demonstrated significant ompA-downregulating activity, suggests that superior antibiofilm activity of this chalcone against the tested dual-species community of A. baumannii is mediated through the OmpA.
Meadowsweet (Filipendula ulmaria (L.) Maxim.) and dropwort (Filipendula vulgaris Moench) are herbaceous perennials employed in folk medicine for their antirheumatic, antipyretic and anti-ulcer ...properties.
To assess ethnomedicinal claims through investigation of antioxidant, anti-inflammatory and gastroprotective effects of F. ulmaria and F. vulgaris lyophilized flower infusions (LFIs) as well as the F. vulgaris isolated flavonoids spiraeoside, kaempferol 4′-O-glucoside, astragalin 2′-O-gallate, mixture of hyperoside 2′-O-gallate and isoquercitrin 2′-O-gallate, and a tannin tellimagrandin II.
Free radical scavenging activity of the tested samples was determined by examining their ability to neutralize DPPH and OH radicals in vitro, whereas reducing properties were assessed in Ferric Reducing Antioxidant Power (FRAP) assay. Anti-inflammatory activity was studied ex vivo in human platelets by monitoring the effect on eicosanoid biosynthesis. Gastroprotective action was estimated in animal model of acute gastric injury induced by ethanol.
LFIs and spiraeoside exerted activities comparable to those of positive control in DPPH-radical scavenging and FRAP antioxidant assays, whereas notable hydroxyl radical scavenging ability was demonstrated only for spiraeoside (IC50 = 5.1μg/mL). Among tested samples, astragalin 2″-O-gallate (IC50 = 141.1μg/mL) and spiraeoside (IC50 = 4.69μg/mL) the most markedly inhibited production of pro-inflammatory prostaglandin E2 and 12(S)-hydroxy-(5Z,8Z,10E,14Z)-eicosatetraenoic acid in human platelets, respectively. Examination of LFIs (100–300mg/kg, p.o.) gastroprotective action in rats revealed their capacity to preserve mucosal integrity. In addition, spiraeoside (50mg/kg, p.o.) and tellimagrandin II (40mg/kg, p.o.) showed ulcer preventive ability.
Current study supports documented traditional use of investigated herbs and indicates that flavonoid and tannin components are partially responsible for the demonstrated pharmacological activities.
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The aim of this study was to test the potential of high molecular weight exopolysaccharide (EPS) produced by the putative probiotic strain
BGCG11 (EPS CG11) to alleviate inflammatory pain in Wistar ...rats. The EPS CG11 was isolated from bacterial surface and was subjected to Fourier-transform infrared spectroscopy (FTIR) and thermal analysis. FTIR spectra confirmed the polysaccharide structure of isolated sample, while the thermal methods revealed good thermal properties of the polymer. The antihyperalgesic and antiedematous effects of the EPS CG11 were examined in the rat model of inflammation induced by carrageenan injection in hind paw. The results showed that the intraperitoneal administration of EPS CG11 produced a significant decrease in pain sensations (mechanical hyperalgesia) and a paw swelling in a dose-dependent manner as it was measured using Von Frey anesthesiometer and plethysmometer, respectively. These effects were followed by a decreased expression of
β and
mRNAs in rat's paw tissue suggesting that the antihyperalgesic and antiedematous effects of the EPS CG11 are related to the suppression of inflammatory response. Additionally, we demonstrated that EPS CG11 exhibits immunosuppressive properties in the peritonitis model induced by carrageenan. Expression levels of pro-inflammatory mediators IL-1β, TNF-α and iNOS were decreased, together with the enhanced secretion of anti-inflammatory IL-10 and IL-6 cytokines, while neutrophil infiltration was not changed. To the best of our knowledge, this is the first study which reports an antihyperalgesic effect as the novel property of bacterial EPSs. Given the high demands of pharmaceutical industry for the replacement of commonly used analgesics due to numerous side effects, this study describes a promising natural compound for the future pharmacological testing in the area.
The aim of this study was to investigate the potential of postbiotics originated from
BGHV110 strain (HV110) to counteract acetaminophen (APAP)-induced hepatotoxicity in HepG2 cells. This strain was ...selected according to its autophagy inducing potential, based on previous studies reporting protective role of autophagy in APAP caused cellular damage. Cell viability was assessed using MTT and LDH assays, while autophagy was monitored by qPCR analysis of
,
,
, and
mRNA expression and by Western blot analysis of p62/SQSTM1 and lipidated LC3 accumulation. Our results showed that detrimental effect of APAP on cell viability was suppressed in the presence of HV110 which was linked with increased conversion of LC3 protein and p62/SQSTM1 protein degradation. Additionally, higher
and
mRNA transcription were noticed in cells co-treated with APAP/HV110, simultaneously. In conclusion, this study suggests that HV110 enhances activation of PINK1-dependent autophagy in HepG2 cells and its eventual co-supplementation with APAP could be potentially used for alleviation of hepatotoxic side effects caused by APAP overdose.
•A new family of Se-functionalized 45S5Bioglass®-based scaffolds was synthesized.•45S5Bioglass®-based scaffolds were coated by SeNp or by PLGA with immobilized SeNp.•Uniform distribution of spherical ...SeNps and interconnected porosity were achieved.•Considerable antibacterial activity against Staphylococcus bacteria was exhibited.•As per obtained data, unique combination of desirable properties in one device is expected.
In the bone tissue engineering field, there is a growing interest in the application of bioactive glass scaffolds (45S5Bioglass®) due to their bone bonding ability, osteoconductivity and osteoinductivity. However, such scaffolds still lack some of the required functionalities to enable the successful formation of new bone, e.g. effective antibacterial properties. A large number of studies suggest that selenium (Se) has significant role in antioxidant protection, enhanced immune surveillance and modulation of cell proliferation. Selenium nanoparticles (SeNp) have also been reported to possess antibacterial as well as antiviral activities. In this investigation, uniform, stable, amorphous SeNp have been synthesized and additionally immobilized within spherical PLGA particles (PLGA/SeNp). These particles were used to coat bioactive glass-based scaffolds synthesized by the foam replica method. Samples were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS) and transmission electron microscopy (TEM). SeNp, 45S5Bioglass®/SeNp and 45S5Bioglass®/PLGA/SeNp showed a considerable antibacterial activity against Gram positive bacteria, Staphylococcus aureus and Staphylococcus epidermidis, one of the main causative agents of orthopedic infections. The functionalized Se-coated bioactive glass scaffolds represent a new family of bioactive, antibacterial scaffolds for bone tissue engineering applications.
Dry MeOH extract of Ferula heuffelii (Apiaceae) underground parts was tested for spasmolytic, gastroprotective and antioxidant activities. HPLC analysis revealed that chlorogenic acid (CGA; 34.6 ...mg/g) was its main constituent. Extract in vitro exhibited notable total antioxidant activity (FRAP value=1.0 μmol Fe2+/mg), and scavenging of DPPH (SC50=62.5 μg/ml) and •OH radicals (49.5 % at 20 μg/ml in 2‐deoxyribose assay). In vitro on isolated rat ileum, extract exhibited significant spasmolytic activity, i. e., it showed 124.6 % of maximal atropine effect on spontaneous contractions (at 100 μg/ml), and reduced spasmogenic effect of KCl (80 mm) to 44.4 % (at 60 μg/ml) and of highest applied concentration of ACh to 26.3 % (at 120 μg/ml). In parallel experiments, spasmolytic effect of CGA was also demonstrated. In acute EtOH‐induced gastric ulceration model in rats, extract (100 mg/kg p.o.) showed significant gastroprotective effect (gastric damage score 0.50), similar to ranitidine (20 mg/kg p.o.). Obtained results showed that tested F. heuffelii polar extract represents new herbal preparation with potential use against some gastrointestinal complaints.
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