Search Results (26)

Green nanotechnology offers a sustainable and eco-friendly approach for nanoframework synthesis. The present study intended to synthesize a novel eco-friendly encapsulated Zeolitic Imidazolate Framework-8 (ZIF-8) in a one-pot method using metabolites from the mangrove plant Conocarpus erectus (CE). Gas Chromatography–Mass Spectrometry (GC-MS) analysis of the extract revealed the presence of important bioactive metabolites. The synthesized material was evaluated by UV-Vis spectroscopy, X-ray diffraction (XRD), particle size analysis (PSA), zeta potential measurement, high-resolution transmission electron microscopy (HR-TEM), and Fourier transform infrared (FT-IR) spectroscopy studies. The environment-friendly mangrove metabolites aided by Zeolitic Imidazolate Framework-8 was found to be crystalline, rhombic dodecahedron structured, and size dispersed without agglomeration. The nanomaterial possessed a broad antimicrobial effect on drug-resistant microorganisms, including Candida krusei, Escherichia coli, Streptococcus Sp., Staphylococcus aureus, Enterococcus Sp., Pseudomonas aeruginosa, Klebsiella pneumoniae, C. propicalis, and C. albicans. Further, its cytotoxicity against MDA-MB-231 cells was found to be efficient. The morphological alterations exhibited by the antiproliferative impact on the breast cancer cell line were detected using DAPI and AO/EB staining. Therefore, ZIF-8 encapsulated mangrove metabolites could serve as an effective biomaterial with biomedical properties in the future. Full article

Background: The aims of this paper are to examine the impact of the COVID-19 pandemic on the non-rational use of antibiotics and potential alterations in the antibiotic resistance profiles of multi-drug resistant (MDR) isolates of Klebsiella pneumoniae (KPN), Pseudomonas aeruginosa (PAE), and Acinetobacter baumannii (ABA). Material and Methods: This study was conducted at the tertiary University Hospital “Dr Dragisa Misovic-Dedinje” (Belgrade, Serbia) and was divided into three periods: pre-pandemic (1.4.2019–31.3.2020, period I), COVID-19 pandemic (1.4.2020–31.3.2021, period II), and COVID-19 pandemic-second phase (1.4.2021–31.3.2022, period III). Cultures were taken from each patient with clinically suspected infection (symptoms, biochemical markers of infection). All departments of the hospital were included in this study. Based on the source, all microbiological specimens were divided into 1° blood, 2° respiratory tract (tracheal aspirate, bronchoalveolar lavage fluid, throat, sputum), 3° central-line catheter, 4° urine, 5° urinary catheter, 6° skin and soft tissue, and 6° other (peritoneal fluid, drainage sample, bioptate, bile, incisions, fistulas, and abscesses). After the isolation of bacterial strains from the samples, an antibiotic sensitivity test was performed for each individual isolate with the automated Vitek^® 2 COMPACT. Antibiotic consumption testing was performed by the WHO guideline equations (ATC/DDD). Results: A total of 2196 strains of KPN, PAE, and ABA from 41,144 hospitalized patients were isolated (23.6% of the number of total isolates). The number of ABA isolates statistically increased (p = 0.021), while the number of PAE isolates statistically decreased (p = 0.003) during the pandemic. An increase in the percentage of MDR strains was observed for KPN (p = 0.028) and PAE (p = 0.027). There has been an increase in the antibiotic resistance of KPN for piperacillin–tazobactam, the third and fourth generations of cephalosporins (ceftriaxone, ceftazidime, and cefepime), all carbapanems (imipenem, meropenem, and ertapenem), and levofloxacin; of PAE for imipenem; and of ABA for amikacin. Total antibiotic consumption increased (from 755 DBD to 1300 DBD, +72%), especially in the watch and reserve group of antibiotics. The highest increases were noted for vancomycin, levofloxacin, azithromycin, and meropenem. MV positively correlated with the increased occurrence of MDR KPN (r = 0.35, p = 0.009) and MDR PAE (r = 0.43, p = 0.009) but not for MDR ABA (r = 0.09, p = 0.614). There has been a statistically significant increase in the Candida sp. isolates, but the prevalence of Clostridium difficile infection remained unchanged. Conclusions: The COVID-19 pandemic has influenced the increase in total and MDR strains of KPN, ABA, and PAE and worsened their antibiotic resistance profiles. An increase in the consumption of both total and specific antibiotics was observed, mostly of fluoroquinolones and carbapenems. A positive correlation between the number of patients on MV and an increase in MDR KPN and MDR PAE strains was noted. It is necessary to adopt and demand the implementation of appropriate antimicrobial stewardship interventions to decrease the resistance of intrahospital pathogens to antibiotics. Full article

The worldwide increase in antifungal resistance, particularly in Candida sp., requires the exploration of novel therapeutic agents. Natural compounds have been a rich source of antimicrobial molecules, where peptides constitute the class of the most bioactive components. Therefore, this study looks into the target-specific binding efficacy of insect-derived antifungal peptides (n = 37) as possible alternatives to traditional antifungal treatments. Using computational methods, namely the HPEPDOCK and HDOCK platforms, molecular docking was performed to evaluate the interactions between selected key fungal targets, lanosterol 14-demethylase, or LDM (PDB ID: 5V5Z), secreted aspartic proteinase-5, or Sap-5 (PDB ID: 2QZX), N-myristoyl transferase, or NMT (PDB ID: 1NMT), and dihydrofolate reductase, or DHFR, of C. albicans. The three-dimensional peptide structure was modelled through the PEP-FOLD 3.5 tool. Further, we predicted the physicochemical properties of these peptides through the ProtParam and PEPTIDE 2.0 tools to assess their drug-likeness and potential for therapeutic applications. In silico results show that Blap-6 from Blaps rhynchopeter and Gomesin from Acanthoscurria gomesiana have the most antifungal potential against all four targeted proteins in Candida sp. Additionally, a molecular dynamics simulation study of LDM-Blap-6 was carried out at 100 nanoseconds. The overall predictions showed that both have strong binding abilities and are good candidates for drug development. In in vitro studies, Gomesin achieved complete biofilm eradication in three out of four Candida species, while Blap-6 showed moderate but consistent reduction across all species. C. tropicalis demonstrated relative resistance to complete eradication by both peptides. The present study provides evidence to support the antifungal activity of certain insect peptides, with potential to be used as alternative drugs or as a template for a new synthetic or modified peptide in pursuit of effective therapies against Candida spp. Full article

The Red Sea is the home of a rich diversity of sponge species with unique ecological adaptations that thrive in its saline, warm, and nutrient-poor waters. Red Sea sponges offer potential as sources of bioactive compounds and novel drugs. The organic extract of the Red Sea sponge Agelas sp. aff. marmarica was investigated for its antimicrobial constituents. Through bioassay-guided fractionation of the antimicrobial fraction of the extract on SiO₂ and Sephadex LH-20, as well as HPLC purification, three bioactive compounds, marmaricines A-C (1–3), were isolated. Structural elucidation of the compounds was performed using 1D (¹H and ¹³C) and 2D (COSY, HSQC, HMBC, and NOESY) NMR, as well as (+)-HRESIMS, leading to the identification of the compounds. The antimicrobial activities of the compounds were assessed through evaluation of their inhibition zones, MIC, MBC, and MFC, against Methicillin-Resistant Staphylococcus aureus (MRSA), Escherichia coli, and Candida albicans. Marmaricines A and B exhibited the strongest antibacterial effects against MRSA, with inhibition zones ranging from 14.00 to 15.00 mm, MIC values of 8 µg/mL, and MBC values of 16 µg/mL. In comparison, marmaracine C showed slightly weaker activity (inhibition zone: 12 mm, MIC: 16 µg/mL, MBC: 32 µg/mL). In terms of antifungal activity, marmaricines B and C demonstrated the greatest effect against C. albicans, with inhibition zones of 14–15 mm, MIC values of 8 µg/mL, and MFCs of 16 µg/mL. Interestingly, none of the compounds showed any inhibitory effect against E. coli. The results indicate that marmaricines A-C are selectively active against MRSA, and marmaricines B and C demonstrate potential against C. albicans, making them promising candidates for the development of novel antimicrobial agents targeting resistant pathogens. Full article

Microbiological communities have a significant impact on health and disease. Candida are ubiquitous fungal pathogens that colonize the mucosal surfaces of the genital, urinary, respiratory, and gastrointestinal tracts, as well as the oral cavity. If the immune system is inadequate, then Candida infections may pose a significant threat. Due to the limited number of clinically approved drugs for the treatment of Candida albicans-based infections and the rapid emergence of resistance to the existing antifungals, a novel series of isoxazole-based derivatives was synthesized and evaluated in vitro for their anti-Candida potential. Two compounds, PUB14 and PUB17, displayed selective antifungal activity without negatively affecting beneficial microbiota, such as Lactobacillus sp., at the same time. Moreover, these compounds exhibited significantly lower cytotoxicity in comparison to conventionally applied local antimicrobial (octenidine dihydrochloride), indicating their potential for safe and effective clinical application in conditions such as vulvovaginal candidiasis. The selective antifungal activity of PUB14 and PUB17 against C. albicans, coupled with its absence of antibacterial effects and minimal cytotoxicity towards HeLa cells, suggests a targeted mechanism of action that warrants further investigation. Consideration of the need to search for new antifungal agents and the discovery of an antifungal potential drug that does not inhibit lactobacilli growth could be a potential strategy to prevent and combat vulvovaginal candidiasis. This striking capacity to eradicate biofilm formed by Candida reveals a new approach to eradicating biofilms and sheds light on isoxazole-based derivatives as promising anti-biofilm drugs. Full article

Background/Objectives: This study evaluates the effect of Mn(II) and Co(II) ions on the production of anti-Candida metabolites by the endophytic fungus Aspergillus sp., isolated from Dizygostemon riparius. The objective was to identify metal-induced secondary metabolites with antifungal potential against drug-resistant Candida species. Methods: Aspergillus sp. was cultivated in Czapek agar supplemented with MnCl₂ (400 µM) or CoCl₂ (200 µM). Metabolite profiles were analyzed using UHPLC-DAD and LC-ESI-HRMS, followed by structural elucidation via NMR. Antifungal and biofilm inhibition activities were tested against Candida albicans and Candida parapsilosis. Toxicity was assessed using Tenebrio molitor larvae. Results: Key metabolites, including pyrophen, penicillquei B, and fonsecinone B, demonstrated antifungal activity with MIC values of 4.37–280.61 µg/mL. Fonsecinone B exhibited superior biofilm inhibition, surpassing fluconazole in reducing biofilm biomass and viability. In vivo assays showed low toxicity, with survival rates above 80% at 2× MIC/kg. Conclusions: Mn(II) and Co(II) significantly modulated the production of antifungal metabolites in Aspergillus sp. Fonsecinone B emerged as a promising candidate for antifungal therapy due to its potent activity and low toxicity. These findings support further investigation into the therapeutic potential of metal-induced fungal metabolites for combating drug-resistant Candida infections. Full article

Candida sp. infections are a threat to global health, with high morbidity and mortality rates due to drug resistance, especially in immunocompromised people. For this reason, the search for new alternatives is urgent, and in recent years, a combined therapy with natural compounds has been proposed. Considering the biological potential of isoespintanol (ISO) and continuing its study, the objective of this research was to assess the effect of ISO in combination with the antifungals fluconazole (FLZ), amphotericin B (AFB) and caspofungin (CASP) against clinical isolates of C. tropicalis and to evaluate the cytotoxic effect of this compound in the acute phase (days 0 and 14) and chronic phase (days 0, 14, 28, 42, 56, 70 and 84) in female mice (Mus musculus) of the Balb/c lineage. The results show that ISO can potentiate the effect of FLZ, AFB and CASP, showing synergism with these antifungals. An evaluation of the mice via direct observation showed no behavioral changes or variations in weight during treatment; furthermore, an analysis of the cytokines IFN-γ and TNF in plasma, peritoneal cavity lavage (PCL) and bronchoalveolar lavage (BAL) indicated that there was no inflammation process. In addition, histopathological studies of the lungs, liver and kidneys showed no signs of toxicity caused by ISO. This was consistent with an analysis of oxaloacetic transaminases (GOT) and pyruvic transaminases (GPT), which remained in the standard range. These findings indicate that ISO does not have a cytotoxic effect at the doses evaluated, placing it as a monoterpene of interest in the search for compounds with pharmacological potential. Full article

Due to their richness in organic substances and nutrients, seaweed (macroalgae) harbor a large number of epiphytic bacteria on their surfaces. These bacteria interact with their host in multiple complex ways, in particular, by producing chemical compounds. The released metabolites may have biological properties beneficial for applications in both industry and medicine. In this study, we assess the diversity of culturable bacterial community of the invasive alga Codium fragile ssp. fragile with the aim to identify key groups within this epiphytic community. Seaweed samples were collected from the Northern Tunisian coast. A total of fifty bacteria were isolated in pure culture. These bacterial strains were identified by amplification of the ribosomal intergenic transcribed spacer between the 16S and the 23S rRNA genes (ITS-PCR) and by 16S rRNA sequencing. Antimicrobial activity, biochemical, and antibiotic resistance profile characterization were determined for the isolates. Isolated strains were tested for their antimicrobial potential against human and fish bacterial pathogens and the yeast Candida albicans, using the in vitro drop method. About 37% of isolated strains possess antibacterial activity with a variable antimicrobial spectrum. Ba1 (closely related to Pseudoalteromonas spiralis), Ba12 (closely related to Enterococcus faecium), and Bw4 (closely related to Pseudoalteromonas sp.) exhibited strong antimicrobial activity against E. coli. The isolated strain Ba4, closely related to Serratia marcescens, demonstrated the most potent activity against pathogens. The susceptibility of these strains to 12 commonly used antibiotics was investigated. Majority of the isolates were resistant to oxacillin, cefoxitin, tobramycin, and nitrofurantoin. Ba7 and Ba10, closely related to the Vibrio anguillarum strains, had the highest multidrug resistance profiles. The enzymes most commonly produced by the isolated strains were amylase, lecithinase, and agarase. Moreover, nine isolates produced disintegration zones around their colonies on agar plates with agarolitic index, ranging from 0.60 to 2.38. This investigation highlighted that Codium fragile ssp. fragile possesses an important diversity of epiphytic bacteria on its surface that could be cultivated in high biomass and may be considered for biotechnological application and as sources of antimicrobial drugs. Full article

Cancer is a threatening disease that needs strong therapy with fewer side effects. A lot of different types of chemotherapy or chemo-drugs are used in cancer treatments but have many side effects. The increasing number of antibiotic-resistant microorganisms requires more study of new antimicrobial compounds and delivery and targeting strategies. This work aims to isolate and identify Azotobacter sp., and extract alginate from Azotobacter sp. As well as fabricating selenium nanoparticles using ascorbic acid as reducing agent (As/Se-NPs), and loading extracted alginate with selenium nanoparticles (Alg-Se-NCMs). The As/Se-NPs and Alg-Se-NCMs were categorized by TEM, EDX, UV–Vis spectrophotometry, FT-IR, and zeta potential. The antifungal activities of both As/Se-NPs and Alg-Se-NCMs were investigated against some human pathogen fungi that cause skin infection such as Aspergillus niger (RCMB 002005), Aspergillus fumigatus (RCMB 002008), Cryptococcus neoformans (RCMB 0049001), Candida albicans (RCMB 005003), and Penicillium marneffei (RCMB 001002). The anticancer activities were determined against HCT-116 colorectal cancer and Hep G2 human liver cancer cells. UV spectra of As/Se-NPs and Alg-Se-NCMs confirmed a surface plasmon resonance at 269 and 296 nm, and zeta potential has negative charges −37.2 and −38.7 mV,. Both As/Se-NPs and Alg-Se-NCMs were hexagonal, size ranging from 16.52 to 97.06 and 17.29 to 44.2. Alg-Se-NCMs had anticancer activities against HCT-116 and HepG2. The Alg-Se-NCMs possessed the highest antifungal activities against Cryptococcus neoformans, followed by Aspergillus niger, but did not possess any activities against Penicillium marneffei. Alginate-capped selenium nanoparticles can be used as antifungal and anticancer treatments. Full article

Candida auris is an emerging Candida sp. that has rapidly spread all over the world. The evidence regarding its origin and emerging resistance is still unclear. The severe infection caused by this species results in significant mortality and morbidity among the elderly and immunocompromised individuals. The development of drug resistance is the major factor associated with the therapeutic failure of existing antifungal agents. Previous studies have addressed the antifungal resistance profile and drug discovery for C. auris. However, complete coverage of this information in a single investigation is not yet available. In this review, we have mainly focused on recent developments in therapeutic strategies against C. auris. Based on the available information, several different approaches were discussed, including existing antifungal drugs, chemical compounds, essential oils, natural products, antifungal peptides, immunotherapy, antimicrobial photodynamic therapy, drug repurposing, and drug delivery systems. Among them, synthetic chemicals, natural products, and antifungal peptides are the prime contributors. However, a limited number of resources are available to prove the efficiency of these potential therapies in clinical usage. Therefore, we anticipate that the findings gathered in this review will encourage further in vivo studies and clinical trials. Full article

Considering the escalating resistance to conventional antifungal medications, it is critical to identify novel compounds that can efficiently counteract this challenge. The purpose of this research was to elucidate the fungicidal properties of secondary metabolites derived from Arcangelisia flava, with a specific focus on their efficacy against Candida species. This study utilized a combination approach comprising laboratory simulations and experiments to discern and evaluate the biologically active constituents present in the dichloromethane extract of A. flava. The in vitro experiments demonstrated that compounds 1 (palmatine) and 2 (fibraurin) exhibited antifungal properties. The compounds exhibited minimum inhibitory concentrations (MICs) ranging from 15.62 to 62.5 µg/mL against Candida sp. Moreover, compound 1 demonstrated a minimum fungicidal concentration (MFC) of 62.5 µg/mL against Candida glabrata and C. krusei. In contrast, compound 2 exhibited an MFC of 125 µg/mL against both Candida species. Based on a molecular docking study, it was shown that compounds 1 and 2 have a binding free energy of −6.6377 and −6.7075 kcal/mol, respectively, which indicates a strong affinity and specificity for fungal enzymatic targets. This study utilized pharmacophore modeling and Density Functional Theory (DFT) simulations to better understand the interaction dynamics and structural properties crucial for antifungal activity. The findings underscore the potential of secondary metabolites derived from A. flava to act as a foundation for creating novel and highly efficient antifungal treatments, specifically targeting fungal diseases resistant to existing treatment methods. Thus, the results regarding these compounds can provide references for the next stage in antifungal drug design. Further investigation is necessary to thoroughly evaluate these natural substances’ clinical feasibility and safety characteristics, which show great potential as antifungal agents. Full article

Antibiotics play a crucial role in preserving and improving public health, saving millions of lives every year. However, their effectiveness is currently under threat due to the ability of bacteria to adapt and develop resistance to these treatments. Therefore, this study was carried out on two soil samples collected in two areas of Arba Aounate, Sidi Bennour province, Morocco, to identify natural antibiotic-producing Actinobacteria capable of combating multi-drug-resistant (MDR) bacteria. A primary screening revealed that of the 50 isolates, 16 exhibited antimicrobial activity against Pseudomonas aeruginosa ATCC 27,853, Staphylococcus aureus ATCC 25,923, Escherichia coli ATCC 25,922, and Candida albicans ATTC 60193. A secondary screening showed that of the 16 isolates, only EIZ1 and EIZ2 isolates displayed outstanding antimicrobial and antifungal activity against 6 MDR bacteria, including Escherichia coli 19L2418, Listeria monocytogenes, Proteus sp. 19K1313, Klebsiella pneumoniae 19K 929, Proteus vulgaris 16C1737, and Klebsiella pneumoniae 20B1572. These two isolates were also characterized culturally, morphologically, physiologically, and biochemically. Afterward, the amplification of 16S rRNA revealed that isolate EIZ2 was 99.06% strongly related to the genus Streptomyces. Furthermore, this extract exhibits strong antioxidant activity against DPPH and ABTS free radicals and elevated ferric-reducing antioxidant power. A significant (p < 0.0001) positive correlation was observed between antioxidant activities and total phenolic and flavonoid contents. A GC–MS analysis of the ethyl acetate extract revealed the presence of 10 compounds, mainly diethyl phthalate (97%) and benzeneacetic acid (94%). This research demonstrates that Streptomyces sp. strain EIZ2 represents a potential source of antimicrobial and antioxidant compounds. These compounds could offer considerable potential as therapeutic agents, paving the way for future developments in medical applications. Full article

Two new 4-hydroxy-2-pyridone alkaloids furanpydone A and B (1 and 2), along with two known compounds N-hydroxyapiosporamide (3) and apiosporamide (4) were isolated from the endophytic fungus Arthrinium sp. GZWMJZ-606 in Houttuynia cordata Thunb. Furanpydone A and B had unusual 5-(7-oxabicyclo[2.2.1]heptane)-4-hydroxy-2-pyridone skeleton. Their structures including absolute configurations were determined on the basis of spectroscopic analysis, as well as the X-ray diffraction experiment. Compound 1 showed inhibitory activity against ten cancer cell lines (MKN-45, HCT116, K562, A549, DU145, SF126, A-375, 786O, 5637, and PATU8988T) with IC₅₀ values from 4.35 to 9.72 µM. Compounds 1, 3 and 4 showed moderate inhibitory effects against four Gram-positive strains (Staphylococcus aureus, methicillin-resistant S. aureus, Bacillus Subtilis, Clostridium perfringens) and one Gram-negative strain (Ralstonia solanacarum) with MIC values from 1.56 to 25 µM. However, compounds 1–4 showed no obvious inhibitory activity against two Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) and two pathogenic fungi (Candida albicans and Candida glabrata) at 50 µM. These results show that compounds 1–4 are expected to be developed as lead compounds for antibacterial or anti-tumor drugs. Full article

Opportunistic pathogen Candida albicans causes systemic infections named candidiasis. Due to the increasing number of multi-drug resistant clinical isolates of Candida sp., currently employed antifungals (e.g., azoles) are insufficient for combating fungal infection. One of the resistance mechanisms toward azoles is increased expression of plasma membrane (PM) transporters (e.g., Cdr1p), and such an effect was observed in C. albicans clinical isolates. At the same time, it has been proven that a decrease in PMs sphingolipids (SLs) content correlates with altered sensitivity to azoles and diminished Cdr1p levels. This indicates an important role for SL in maintaining the properties of PM and gaining resistance to antifungal agents. Here, we prove using a novel spot variation fluorescence correlation spectroscopy (svFCS) technique that CaCdr1p localizes in detergent resistant microdomains (DRMs). Immunoblot analysis confirmed the localization of CaCdr1p in DRMs fraction in both the C. albicans WT and erg11Δ/Δ strains after 14 and 24 h of culture. We also show that the C. albicanserg11Δ/Δ strain is more sensitive to the inhibitor of SLs synthesis; aureobasidin A (AbA). AbA treatment leads to a diminished amount of SLs in C. albicans WT and erg11Δ/Δ PM, while, for C. albicanserg11Δ/Δ, the general levels of mannose-inositol-P-ceramide and inositol-P-ceramide are significantly lower than for the C. albicans WT strain. Simultaneously, the level of ergosterol in the C. albicans WT strain after adding of AbA remains unchanged, compared to the control conditions. Analysis of PM permeabilization revealed that treatment with AbA correlates with the disruption of PM integrity in C. albicanserg11Δ/Δ but not in the C. albicans WT strain. Additionally, in the C. albicans WT strain, we observed lower activity of H⁺-ATPase, correlated with the delocalization of both CaCdr1p and CaPma1p. Full article

Candida albicans is still the major yeast causing human fungal infections. Nevertheless, in the last decades, non-Candida albicans Candida species (NCACs) (e.g., Candida glabrata, Candida tropicalis, and Candida parapsilosis) have been increasingly linked to Candida sp. infections, mainly in immunocompromised and hospitalized patients. The escalade of antifungal resistance among Candida sp. demands broadly effective and cost-efficient therapeutic strategies to treat candidiasis. Marine environments have shown to be a rich source of a plethora of natural compounds with substantial antimicrobial bioactivities, even against resistant pathogens, such as Candida sp. This short review intends to briefly summarize the most recent marine compounds that have evidenced anti-Candida sp. activity. Here, we show that the number of compounds discovered in the last years with antifungal activity is growing. These drugs have a good potential to be used for the treatment of candidiasis, but disappointedly the reports have devoted a high focus on C. albicans, neglecting the NCACs, highlighting the need to perform outspreading studies in the near future. Full article