Search Results (279)

Herbal medicines can be promising for the treatment of infections caused by multidrug-resistant microorganisms. This study aimed to evaluate Rosmarinus officinalis (Rosemary) hydroalcoholic extract (RHE) regarding its phytochemical composition and potential for eliminating polymicrobial biofilm of Candida albicans with multidrug-resistant bacteria (Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa). The extraction and quantification of the extract (flavonoids and phenols) were performed, and its antioxidant activity (DPPH) and the presence of bio-active compounds were investigated using high-performance liquid chromatography with Diode Array Detection (HPLC-DAD) and Gas Chromatography–Mass Spectrometry (GC-MS). The minimum inhibitory concentration (MIC) and minimum microbicidal concentration (MMC) were determined, and the extract’s action on polymicrobial biofilms was evaluated using the MTT assay. Data were analyzed using one-way ANOVA and Tukey’s tests, as well as Kruskal–Wallis and Dunn’s tests, with a significance level of 5%. RHE showed compatible amounts of flavonoids and phenols, with an EC50 of 19.53 µg/mL. Through HPLC-DAD and GC-MS, biomolecules such as rosmarinic acid and α-Pinene were identified. The extract exhibited microbicidal activity and antibiofilm action, with reduction percentages of up to 69.6% (p < 0.05), showing superior performance compared to 0.12% chlorhexidine against C. albicans + A. baumannii. In conclusion, RHE may be a promising therapeutic agent against multidrug-resistant pathogens. Full article

Background: Assessment of efficacy in HIV prevention trials remains a challenge in the era of widespread use of active controls. We investigated use of counterfactual groups to assess treatment efficacy. Methods: We used data from placebo arms of two previous HIV prevention efficacy trials (Pro2000 vaginal microbicide trial, 2005–2009: ISRCTN64716212 and dapivirine vaginal ring trial, 2013–2016: NCT01539226) and four observational cohorts (two in each of the periods; (a) during the conduct of a simulated HIV vaccine efficacy trial (SiVET), 2012–2017, and (b) prior to SiVET (2005–2011)) and compared HIV prevention efficacy trial targeted outcomes with SiVETs. SiVET participants were administered a licensed hepatitis B vaccine at 0, 1 and 6 months mimicking an HIV vaccine efficacy trial schedule. Participants were tested for HIV quarterly for one year. The probability of the SiVET assignment conditioned on the measured participants’ baseline characteristics were estimated using propensity scores (PS) and matched between SiVET and placebo arm of trials. Similar calculations were repeated for observational cohorts in the pre- and during SiVET periods. We compared HIV incidence rate ratio (IRR) between SiVET and the trials or observational data before and after PS matching. Results: This analysis involved data from 3387 participants; observational cohorts before SiVET 1495 (44.2%), placebo arms of previous trials 367 (10.8%), observational cohorts during SiVET conduct 953 (28.1%) and SiVETs 572 (16.9%). Before propensity score matching (PSM), there were significant imbalances in participants’ baseline characteristics between SiVET, and all the other studies and HIV incidence was lower in SiVET. After PSM, the participants’ characteristics were comparable. The HIV incidence in SiVET was similar to that in the previous trial, IRR = 1.01 95% CI: 0.16–4.70), p = 0.968, and observational data during SiVET, IRR = 0.74, 95% CI 0.34–1.54), p = 0.195, but much lower compared to the observational data pre-SiVET, IRR = 0.48, 95% CI: 0.20–1.04), p = 0.023. Conclusions: PSM can be used to create counterfactual groups from other data sources. The best counterfactual group for assessing treatment effect is provided by data collected in the placebo arm of previous trials followed by that from observational data collected concurrently to the current trial (SiVET). Even with PSM, observational data collected prior to the current trial may overestimate treatment effect. Full article

The emergence and spread of antimicrobial resistance among pathogens are significantly reducing available therapeutic options, highlighting the urgent need for novel and complementary treatment strategies. Antimicrobial photodynamic therapy (aPDT) is a promising alternative approach that can overcome antimicrobial resistance through a multitarget mechanism of action, exerting direct bactericidal and fungicidal effects with minimal risk of resistance development. Although aPDT has shown efficacy against a variety of pathogens, data on its activity against large collections of clinical multidrug-resistant strains are still limited. In this study, we assessed the antimicrobial activity of the photosensitizer RLP068/Cl combined with a red light-emitting LED source at 630 nm (Molteni Farmaceutici, Italy) against a large panel of Gram-negative and Gram-positive bacterial strains harboring relevant resistance traits and Candida species. Our results demonstrated the significant microbicidal activity of RLP068/Cl against all of the tested strains regardless of their resistance phenotype, with particularly prominent activity against Gram-positive bacteria (range of bactericidal concentrations 0.05–0.1 µM), which required significantly lower exposure to photosensitizer compared to Candida and Gram-negative species (range 5–20 µM). Overall, these findings support the potential use of RLP068/Cl-mediated aPDT as an effective therapeutic strategy for the management of localized infections caused by MDR organisms, particularly when conventional therapeutic options are limited. Full article

Metal oxide nanoparticles (NPs) are known to have biological activity against various microorganisms; thus, they have been widely used as microbicidal agents, and their use poses potential solutions to problems such as biofouling. This study focuses on the surface modification of TiO₂ and ZrO₂ nanoparticles with lactic acid (LA) and stearic acid (SA) to enhance their antibacterial activity (AA). The surface modification of TiO₂ and ZrO₂ nanoparticles was performed using continuous frequency ultrasound. Sonication was performed at different reaction times. Characterization of the modified nanoparticles by TGA, DSC, XRD, FTIR, and XPS techniques demonstrated the presence of the organic ligand on the surface of the nanoparticles. The surface modification results in a reduction in the crystal size of the nanoparticles. Regarding the antibacterial properties of modified TiO₂ and ZrO₂ nanoparticles, their minimum bactericidal concentration (MBC) against Gram-negative and Gram-positive bacteria of the bacterial strains Escherichia coli and Staphylococcus aureus was evaluated. The results obtained from the AA of the modified and unmodified nanoparticles demonstrated greater efficacy of the modified nanoparticles, in the particular case of TiO₂ and TiO₂-LA, evaluated at concentrations of 200, 500, 800, 1100, and 1400 ppm, TiO₂-LA nanoparticles showed better results at most of the concentrations studied and a bacterial inhibition percentage of 99.0% was achieved at a concentration of 500 ppm against the Escherichia coli bacteria, while TiO₂ NPs only reached 55.0%, this shows that ligands with more than one functional group play an important role in improving AA. Full article

Helicobacter pylori (H. pylori), a prevalent human pathogen affecting nearly half the global population, is a major contributor to chronic gastritis, peptic ulcer, and gastric cancer. H. pylori develops biofilms (BFs) allowing bacteria to evade the immune response. Differences in composition between planktonic and biofilm cells influence the host’s immune response, yet the specific biofilm components modulating this response remain uncharacterized. Considering the above, this study evaluated the effect of in vitro-generated H. pylori BF on the antibacterial activity of neutrophils. This work utilized sonication to obtain disaggregated H. pylori BF (d-BF-Hp) to challenge human neutrophils, assessing their bactericidal and phagocytic activity against Staphylococcus aureus. S. aureus survival in the presence of neutrophils was enhanced by 10 μg/mL of d-BF-Hp’s protein. Conversely, S. aureus survival was significantly lower at 30 µg/mL compared to 10 µg/mL d-BF-Hp. Furthermore, 10 and 30 µg/mL of d-BF-Hp significantly reduced the neutrophil phagocytosis rate. Our findings suggest that d-BF-Hp components diminish neutrophil bactericidal activity, although this effect was not observed at higher d-BF-Hp concentrations. Increased d-BF-Hp concentrations proportionally reduced neutrophil phagocytic capacity. Future work should explore the mechanisms underlying the alteration of neutrophil microbicidal properties. Full article

Nanobiotechnology applications in plant tissue culture have improved the development and physiology of explants, resulting in plants with high genetic homogeneity and phytosanitary quality. Silver nanoparticles (AgNPs) are well-known for their microbicidal properties, but their biochemical effects on plants require further exploration. In this work, green-synthesized AgNPs were evaluated in strawberry in vitro culture, photosynthetic pigment production, and acclimatization. AgNPs produced by Lysinibacillus fusiformis were characterized. Strawberry explants were grown in vitro on MS medium with 0, 100, 200, and 300 mg L⁻¹ AgNPs at 24 ± 2 °C and a photoperiod of 16:8 h light/dark. Shoot height and number, number of leaves, number of roots, and root length were evaluated, and chlorophyll (a, b, and total) was quantified. Rooted shoots were acclimatized ex vitro on substrates containing 0 and 200 mg L⁻¹ AgNPs. The results showed that low AgNPs concentrations had a positive impact on shoot multiplication, development, and rooting, but at higher concentrations, the effects decayed. However, chlorophyll production improved with increasing AgNP concentration. Shoots treated with AgNPs showed higher ex vitro survival. Our study has direct implications for the profitability and sustainability of commercial strawberry production. Full article

Background and Objectives: Successful endodontic treatment requires thorough disinfection and removal of the smear layer to prevent reinfection. However, conventional irrigants like sodium hypochlorite (NaOCl) and ethylenediaminetetraacetic acid (EDTA) can compromise dentin integrity. This study assessed the efficacy of the Synergistic Microbicidal and Ablative Root canal Technique (SMART), which integrates AromaRoot, a biocompatible irrigation solution based on quaternary ammonium compounds, with 980 nm diode laser activation, to enhance bacterial reduction and smear layer removal. Materials and Methods: Sixty extracted single-rooted human teeth were inoculated with Enterococcus faecalis and divided into four treatment groups using NaOCl, AromaRoot, and 980 nm laser, either alone or in combination. Bacterial counts were measured as colony-forming units per milliliter (CFU/mL). For smear layer analysis, 56 extracted teeth were prepared and irrigated using EDTA, AromaRoot, and laser activation, followed by scanning electron microscopy to evaluate dentinal tubule exposure. Data were analyzed using Kruskal–Wallis and ANOVA. Results: The combination of AromaRoot, NaOCl, and laser activation achieved a 99.00% bacterial reduction (from 8082 to 60 CFU/mL, p < 0.001), outperforming NaOCl alone (98.34%, 131 CFU/mL). For smear layer removal, AromaRoot with laser achieved 78.5% open dentinal tubules in the apical third, significantly higher than EDTA alone (64.5%, p < 0.05), though EDTA remained superior in the coronal third (89.0% vs. 81.0%, p > 0.05). Conclusions: The SMART technique significantly improves both disinfection and smear layer removal in root canal therapy, particularly in the apical region. These findings suggest that AromaRoot, especially when laser-activated, may serve as a safe and effective alternative to conventional irrigants, warranting further clinical evaluation. Full article

We have reviewed the primary literature on the virucidal efficacy of microbicidal active ingredients, formulated microbicides, and physical inactivation approaches (heat, irradiation) for hemorrhagic fever viruses (HFVs) (arenaviruses, filoviruses, flaviviruses, hantaviruses, nairoviruses, and phenuiviruses), and for two non-typical HFV paramyxoviruses. As each of these HFVs are large, lipid-enveloped RNA viruses, their susceptibilities to virucidal agents are informed by the so-called hierarchy of susceptibility of pathogens to microbicides. The unique susceptibility of lipid-enveloped viruses to most classes of microbicides is based on the common mechanisms of action of envelope-disrupting microbicides. Despite this, due to the relatively great lethality of these viruses, it is prudent (where possible) to confirm the expected efficacies of inactivation approaches in testing involving the HFVs themselves (as opposed to less lethal surrogate viruses) using field-relevant methods. Empirical data for virucidal activities of microbicidal active ingredients, formulated microbicides, and physical inactivation approaches, such as heat, ultraviolet light, and gamma irradiation, that were collected specifically for HFVs have been reviewed and summarized in this paper. These empirical data for surface and hand hygiene approaches, liquid inactivation approaches, and approaches for rendering diagnostic samples safe to handle inform non-pharmaceutical interventions intended to mitigate transmission risk associated with these HFVs. Full article

Due to their secondary metabolite content, plant extracts are an alternative method for controlling pathogenic organisms in agriculture and post-harvest operations. Botrytis cinerea and Pseudomonas syringae are among the causative agents of diseases and losses in agricultural production. The species Larrea tridentata is abundant in the arid and semi-arid zones of Mexico and has no defined use; however, it contains secondary metabolites with microbicidal potential that could aid in biological control and enhance its harvest status. Growth inhibition (halo) of B. cinerea and P. syringae was evaluated by applying alcoholic extract of L. tridentata leaves at doses of 50, 100, 250, 500, 750, 1000, and 2000 µg mL⁻¹ in vitro, using poisoned medium and potato dextrose agar for the fungus and the agar well method for the bacteria, in a completely randomized design with five replicates. The flavonoids quercetin, apigenin, narigenin, kaempferol, and galangin were identified as possible agents of microbicidal activity. The extract inhibited the growth of B. cinerea from 100 µg mL⁻¹ and completely inhibited it with 1000 and 2000 µg mL⁻¹. For P. syringae, inhibition was observed from 250 µg mL⁻¹, demonstrating that the higher the concentration, the greater the growth inhibitory effect. The secondary metabolite content of the L. tridentata extract is sufficient to have an impact on microorganisms with economic impact in agriculture. Full article

New roles for immune cells, overcoming the classical cytotoxic response, have been highlighted by growing evidence. The immune cells, such as neutrophils, monocytes/macrophages, and eosinophils, are versatile cells involved in the release of web-like DNA structures called extracellular traps (ETs) which represent a relevant mechanism by which these cells prevent microbes’ dissemination. In this process, many enzymes, such as elastase, myeloperoxidase (MPO), and microbicidal nuclear and granule proteins, which contribute to the clearance of entrapped microorganisms after DNA binding, are involved. However, an overproduction and release of ETs can cause unwanted and dangerous effects in the host, resulting in several pathological manifestations, among which are chronic inflammatory disorders, autoimmune diseases, cancer, and diabetes. In this review, we discuss the release mechanisms and the double-edged sword role of ETs both in physiological and in pathological contexts. In addition, we evaluated some possible strategies to target ETs aimed at either preventing their formation or degrading existing ones. Full article

Antimicrobial resistance is a growing global challenge, rendering many standard treatments ineffective. Essential oils (EOs) of cinnamon (Cinnamomum aromaticum Nees) and clove (Syzygium aromaticum (L.) Merr. et Perry) may offer an alternative solution due to their high antimicrobial properties and their abilities to fight resistant pathogens. This study evaluates the antimicrobial activity of these two EOs, and their synergistic potential when combined with two antibiotics (ciprofloxacin and vancomycin) and two antifungals (fluconazole and amphotericin B) against various bacterial and yeasts strains. The antimicrobial activities of each EO were evaluated by agar diffusion and broth microdilution assays, while the synergetic effects with antimicrobials were determined by calculating the fractional inhibitory concentration index (FICI) using the checkerboard method. The chemical composition of the EOs was analyzed using Gas Chromatography-Mass Spectrometry (GC-MS). The identification of individual components in the EOs was achieved by comparing their mass spectra with the NIST MS Search database and by correlating their retention times with those of known standards. GC-MS analysis revealed that the main constituents of S. aromaticum EO were eugenol (71.49%) and β-caryophyllene (23.43%), while C. aromaticum EO were dominated by cinnamaldehyde (47,04%) and cinnamyl acetate (18.93%). Antimicrobial activity showed that cinnamon EO exhibits highest effectiveness against all tested strains, with inhibition zones (IZ) ranging from 16.99 mm to 53.16 mm, and minimum inhibitory concentrations (MIC) and minimum microbicidal concentrations (MMC) ranging from 0.039 mg/mL to 0.156 mg/mL. However, for clove EO, the IZ ranged from 9.31 mm to 29.91 mm, with MIC and MMC values from 0.313 mg/mL to 1.25 mg/mL. In combination with antibiotics (ciprofloxacin and vancomycin), the studied EOs showed promising synergistic effects with reduction up to 128-fold. As regards antifungals (amphotericin B, and fluconazole), the synergistic effects were recorded with MIC gains up to 32-fold. Our findings demonstrate that the EOs from C. aromaticum and S. aromaticum exhibit significant broad-spectrum antimicrobial activity against diverse yeast and bacterial strains. This highlights their potential as bases for the development of novel plant-based antimicrobial agents. Importantly, the observed synergistic effects of these EOs with conventional antibiotics support their integration into medical treatments as a strategy to address microbial resistance. Future research should aim to elucidate the mechanisms underlying these synergistic actions, optimize their application, and enhance their therapeutic efficacy. Full article

Background/Objectives: This study aims to gain insights into the antimicrobial and antiherpetic activity of hyperforin-rich Hypericum perforatum L. (HP) extract using nanostructured lipid carriers (NLCs) as delivery platforms. Methods: Two established NLC specimens, comprising glyceryl behenate and almond oil or borage oil, and their extract-loaded counterparts (HP-NLCs) were utilized. Their minimal bactericidal/fungicidal concentrations (MBC; MFC) were investigated against Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923, Pseudomonas aeruginosa ATCC 10145, Klebsiella pneumoniae ATCC 10031, and Candida albicans ATCC 10231. The anti-herpesvirus (HSV-1) potential was evaluated concerning antiviral and virucidal activity and impact on viral adsorption. Results: The borage oil-based extract-loaded nanodispersion (HP-NLC2) exhibited pronounced microbicidal activity against S. aureus (MBC 6.3 mg/mL), K. pneumoniae (MBC 97.7 µg/mL), and C. albicans (MFC < 48.8 µg/mL), unlike the almond oil-containing sample (HP-NLC1), which showed only weak inhibition of the fungal growth. HP-NLC2 was found to be less cytotoxic and to suppress HSV-1 replication slightly more than HP-NLC1, but generally, the effects were weak. Neither the empty lipid nanoparticles nor the HP extract-loaded carriers expressed activity against E. coli, P. aeruginosa, the HSV-1 extracellular virions, or viral adhesion. Conclusions: It could be concluded that both HP-NLC samples revealed only minor antiherpetic potential of the hyperforin-rich extract, but HP-NLC2 demonstrated significant antibacterial and antimycotic activity. Therefore, the latter was featured as a more convenient HP-carrier system for nano-designed dermal pharmaceutical formulations. Such a thorough investigation of hyperforin-determined anti-HSV-1 effects and antibacterial and antimycotic properties, being the first of its kind, contributes to the fundamental knowledge of HP and reveals new perspectives for the utilization, limitations, and therapeutic designation of its non-polar components. Full article

Medicinal plants are widely used in Bolivian folk medicine for the treatment of infectious diseases. We have selected one, Clinopodium bolivianum (Benth.) Kuntze, known as “Khoa”, to investigate its potential anti-HIV activity since, traditionally, it has been used to treat other viral infectious diseases. We have carried out an antiviral bioassay-guided fractionation of different extracts of the aerial parts of C. bolivianum. An antiviral crude polysaccharide was obtained, (SBA_S), which is rich in glucose, galactose, mannose, arabinose, xylose, and rhamnose and only has traces of galacturonic acid. SBA_S exhibited antiviral activity with a mechanism of action unrelated to the mannose–lectin DC-SIGN receptors but with a strong viral neutralization activity. In summary, a purified polysaccharide from C. bolivianum has been identified as the main compound responsible for its antiviral activity. SBAs proved to be a neutralizing agent with high antiviral capacity in vitro, so they could be part of new microbicide formulations to prevent HIV transmission. Full article

Quorum quenchers are emerging as an alternative to conventional antimicrobials, since they hinder the development of virulence or resistance mechanisms but without killing the microorganisms, thus, reducing the risk of antimicrobial resistance. Many quorum quenchers are analogs of the natural quorum-sensing signaling molecules or autoinducers. Thus, different analogs of natural N-acylhomoserine lactones (AHLs) have been reported for controlling virulence or reducing the production of biofilms in Gram-negative pathogens. Herein we report the preparation of AHL analogs with a variety of N-substituents in just two steps from readily available N-substituted hydroxyproline esters. The substrates underwent an oxidative radical scission of the pyrrolidine ring. The resulting N-substituted β-aminoaldehyde underwent reduction and in situ cyclization to give a variety of homoserine lactones, with N- and N,N-substituted amino derivatives and with high optical purity. The libraries were screened for the inhibition of violacein production in Chromobacterium violaceum, a Gram-negative pathogen. For the first time, N,N-disubstituted AHL analogs were studied. Several N-sulfonyl derivatives, one carbamoyl, and one N-alkyl-N-sulfonyl homoserine lactone displayed a promising inhibitory activity. Moreover, they did not display microbicide action against S. aureus, C. jejuni, S. enterica, P. aeruginosa, and C. albicans, confirming a pure QQ activity. The determination of structure–activity relationships and in silico ADME studies are also reported, which are valuable for the design of next generations QQ agents. Full article

Biofilms contribute to chronic infections and the development of antimicrobial resistance (AMR). We are developing an antimicrobial blue light (aBL) device to reduce bacterial bioburden in wounds and decrease reliance on systemic antibiotics. aBL induces the generation of reactive oxygen species (ROS) through photoexcitation of endogenous chromophores, causing bacterial damage and death. This study explores the combination of tetracyclines (TCs) with aBL for the treatment of biofilm infections in vitro. Tetracyclines (TCs), including second-generation minocycline (MC), doxycycline (DOCT), and third-generation agents omadacycline (OM) and tigecycline (TG), were evaluated for their ability to enhance bactericidal effects and ROS production during aBL treatment of abiotic biofilm. TCs were tested under dark conditions and with varying aBL light parameters against biofilms of methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa (PA), and Escherichia coli (E. coli). Results showed that TCs alone were ineffective against these biofilm cultures. However, when combined with aBL either before or after TC treatment, significant enhancement of microbicidal activity was observed. When the aBL is added before the TCs, there was equivalent bactericidal effect, indicating that TCs primary action against biofilms were not as photosensitizers. These findings suggest that aBL can significantly enhance the antimicrobial activity of TCs, potentially offering a new effective approach to treating biofilm-associated infections and combating AMR when aBL is applicable. Full article