Search Results (1,147)

This study focuses on the search for new effective synthetic antimicrobial compounds as a tool against the widespread presence of microorganisms resistant to existing drugs. Five derivatives of [1,3]thiazolo[3,2-b][1,2,4]triazoles were synthesized using an accessible protocol based on electrophilic heterocyclization and were characterized using infrared (FTIR) and nuclear magnetic resonance (NMR) spectroscopies, and their in vitro antimicrobial and antifungal activities were evaluated using the agar plate diffusion method and the microdilution plate procedure. Both antibacterial (Gram-positive and Gram-negative) and antifungal activities were found for the examined samples. The minimum inhibitory concentration (MIC) varied from 0.97 to 250 µg/mL, and the minimum bactericidal concentration (MBC) from 1.95 to 500 µg/mL. Compound 2a showed good antifungal action against Candida albicans and Saccharomyces cerevisiae with minimum fungicidal concentration (MFC) 125 and MIC 31.25 µg/mL. The molecular docking revealed that the 2-heptyl-3-phenyl-6,6-trimethyl-5,6-dihydro-3H-[1,3]thiazolo[3,2-b][1,2,4]triazol-7-ium cation stands out as a highly promising candidate for further investigation due to a wide range of interactions, including conventional hydrogen bonds, π–σ, π–π T-shaped, and hydrophobic alkyl interactions. The synthesis and preliminary evaluation of [1,3]thiazolo[3,2-b][1,2,4]triazoles yielded promising antimicrobial and antifungal candidates. The diverse interaction profile of the 2-heptyl derivative salt allows this compound’s selection for further biological studies. Full article

Coinfection poses severe threats to poultry health, particularly due to the complexity and resilience of multispecies interactions, increasing the difficulty of treatment. Haemophilus spp., a heterotrophic bacterium, heavily relies on extracellular growth factors acquired from other organisms or its surrounding environment. Although coinfections by Avibacterium paragallinarum and Bacillus have been reported, the underlying mechanism of the cooperative interaction remains poorly understood. In this study, we characterized the growth-promoting properties and nicotinamide adenine dinucleotide production of some Bacillus species, including probiotic Bacillus, to evaluate the feasibility of A. paragallinarum coinfection in vitro. Meanwhile, we determined the minimum inhibitory concentration (MIC) and population dynamics of cocultured Bacillus and A. paragallinarum to assess the effect of bacterial interactions on antibiotic efficacy. Additionally, we demonstrated that B. cereus aggravates rhinitis symptoms in chickens infected with A. paragallinarum. Our findings reveal that Bacillus spp.-derived metabolites sustain A. paragallinarum growth and enhance its survival, thereby highlighting the infection risks associated with Bacillus colonization in the respiratory tract. Full article

Artemisia serotina Bunge represents one of the endemic Artemisia L. species in flora of Central Asia. There is scant information on the phytochemistry and biological activity of this species. The aim of the present study was to analyze the chemical composition of essential oil from A. serotina (ASEO) growing in south Kazakhstan, together with the determination of its biological activity. ASEO isolation was carried out by hydrodistillation according to the State Pharmacopoeia of the Republic of Kazakhstan. Analysis of GC/MS data revealed that the most characteristic components of ASEO were irregular monoterpenes from three families: santolinane, artemisane, and lavandulane. The major compound was santolina alcohol (34.6%). Antimicrobial activity was studied against the reference bacterial and fungal strains using the recommended methods, allowing for an estimation of MIC (minimum inhibitory concentration). ASEO was most effective against Candida albicans (MIC = 2 mg/mL), exerting fungicidal activity. Thw MIC for bacterial species was higher, i.e., 4–16 mg/mL. Antiviral activity was tested against Coxsackievirus B3 (CVB3) and Human Herpesvirus type 1 (HHV-1) propagated in VERO cells. No antiviral effect against either virus was found at an ASEO concentration of 0.25 mg/mL, but a noticeable decrease in the intensity of HHV-1-related cytopathic effects was observed. Anticancer activity studies included several cancer cell lines. Cytotoxicity, cell cycle, thiol levels, and cell vitality were analyzed. Among the cancer cell lines tested, the breast cancer T47-D cell line exhibited the highest sensitivity to ASEO (IC₅₀ = 40.81 ± 4.21 µg/mL at 24 h; IC₅₀ = 33.17 ± 2.11 µg/mL at 48 h). The anticancer effect was suggested to be mainly due to the induction of cytostatic effects, accompanied by a disturbance of the intracellular redox balance. The obtained data provide novel information on the unique chemical composition of ASEO from south Kazakhstan, representing a new chemotype. Its bioactivity, including promising antifungal and anticancer properties, was demonstrated for the first time. Full article

Background: The antimicrobial peptides (AMPs) SET-M33L and SET-M33L-PEG were investigated against 10 clinical isolates of P. aeruginosa. Methods: Their minimum inhibitory concentrations (MICs), minimum bactericidal concentrations (MBCs), and minimum biofilm inhibitory concentrations (MBICs) were evaluated against tobramycin, ceftazidime, and polymyxin B. Results: MICs and MBCs were 7- to 100-fold lower than tobramycin, and 10- to 300-fold lower than ceftazidime. Fractional inhibitory concentration (FIC) indices showed an additive effect, while fractional bactericidal concentration (FBC) indices showed synergistic effects (FBC < 0.5) for most isolates. Conclusion: SET-M33L and SET-M33L-PEG are promising antimicrobial agents against strong biofilm-forming P. aeruginosa, including MDR isolates. Full article

A previously undescribed cis-clerodane diterpenoid, diangelate solidagoic acid J (1), along with two known cis-clerodane diterpenoids, solidagoic acid C (2) and solidagoic acid D (3), as well as two known unsaturated monoacylglycerols, 1-linoleoyl glycerol (4) and 1-α-linolenoyl glycerol (5), were isolated and characterized from the n-hexane leaf extract of Solidago gigantea (giant goldenrod). Compounds 2–5 were identified first in this species, and compounds 4 and 5 are reported here for the first time in the Solidago genus. The bioassay-guided isolation procedure included thin-layer chromatography (TLC) coupled with a Bacillus subtilis antibacterial assay, preparative flash column chromatography, and TLC–mass spectrometry (MS). Their structures were elucidated via extensive spectroscopic and spectrometric techniques such as one- and two-dimensional nuclear magnetic resonance (NMR) spectroscopy and high-resolution tandem mass spectrometry (HRMS/MS). The antimicrobial activities of the isolated compounds were evaluated by a microdilution assay. All compounds exhibited weak to moderate antibacterial activity against the Gram-positive plant pathogen Clavibacter michiganensis, with MIC values ranging from 17 to 133 µg/mL, with compound 5 being the most potent. Only compound 1 was active against Curtobacterium flaccumfaciens pv. flaccumfaciens, while compound 3 demonstrated a weak antibacterial effect against B. subtilis and Rhodococcus fascians. Additionally, the growth of B. subtilis and R. fascians was moderately inhibited by compounds 1 and 5, respectively. None of the tested compounds showed antibacterial activity against Gram-negative Pseudomonas syringae pv. tomato and Xanthomonas arboricola pv. pruni. No bactericidal activity was observed against the tested microorganisms. Compounds 2 and 3 displayed weak antifungal activity against the crop pathogens Bipolaris sorokiniana and Fusarium graminearum. Our results demonstrate the efficacy of bioassay-guided strategies in facilitating the discovery of novel bioactive compounds. Full article

Antimicrobial resistance is a threat to probiotic microorganisms due to their potential role in harboring and transmitting resistance genes. This study focuses on two Bifidobacterium species (B. animalis subsp. lactis and B. longum) by analyzing 657 Minimal Inhibitory Concentration (MIC) values extracted from research articles indexed in Scopus, PubMed, and Web of Science, published since 2014, and considering 17 different antibiotics. MIC values were used for descriptive statistical analysis (boxplots and violin plots) to evaluate both inter- and intraspecies distributions. The results showed an overall increase in MIC values compared to historical data, with B. longum exhibiting high resistance to tetracyclines and streptomycin—approximately 25% to 50% of the strains had MIC values > EFSA cut-offs. The violin plots revealed the presence of resistant subpopulations, particularly within B. longum. These findings support the relevance of longitudinal MIC analysis as a tool for detecting early shifts in antimicrobial susceptibility and highlight the importance of data-driven approaches for microbiological risk assessment in probiotic applications. Full article

Background: The accumulation of agri-food waste is a major environmental and economic challenge and converting these by-products into bioactive compounds fits within the circular bioeconomy. This study aimed to evaluate the antimicrobial potential of extracts derived from Cannabis sativa L. leaves (CSE), Crocus sativus tepals (CST), and Prunus avium L. cherry waste (VCE) against four key bacterial species (Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa). Methods: Minimum inhibitory concentration (MIC) assays were performed to assess antibacterial activity, while a bioinformatic pipeline was implemented to explore possible molecular targets. Full-proteome multiple sequence alignments across the bacterial strains were used to identify conserved, strain-specific proteins, and molecular docking simulations were applied to predict binding interactions between the most abundant compounds in the extracts and their targets. Results: CSE and CST demonstrated bacteriostatic activity against S. aureus and B. subtilis (MIC = 15.6 mg/mL), while VCE showed selective activity against B. subtilis (MIC = 31.5 mg/mL). CodY was identified as a putative molecular target for CSE and CST, and ChaA for VCE. Docking results supported the possibility of spontaneous binding between abundant extract constituents and the predicted targets, with high binding affinities triggering a strong interaction network with target sensing residues. Conclusions: This study demonstrates the antimicrobial activity of these agri-food wastes and introduces a comprehensive in vitro and in silico workflow to support the bioactivity of these agri-food wastes and repurpose them for innovative, eco-sustainable applications in the biotechnology field and beyond. Full article

This study evaluated the therapeutic potential of 70% ethanol extracts from six medicinal plants (Chenopodium album, Cassia tora, Cudrania tricuspidata, Dioscorea polystachya, Lonicera japonica, Solidago virgaurea subsp. gigantea) through their antibacterial, antioxidant, cytotoxic, and immunomodulatory activities, targeting applications in aquaculture. All extracts exhibited potent antibacterial activity (MIC ≤ 10 μg/mL) against Aeromonas spp. and Photobacterium damselae subsp. damselae, but limited efficacy against Streptococcus parauberis. C. tricuspidata (CTR) and C. tora (CTO) demonstrated superior antioxidant activity (IC₅₀ = 1292 μg/mL and IC₅₀ = 227 μg/mL, respectively), correlating with high polyphenol content (1498 and 1409 mg GAE/g). CTR displayed significant concentration-dependent cytotoxicity (IC₅₀ = 904.2 μg/mL), while C. album (CA) promoted cell proliferation (132.3% viability). In LPS-stimulated CHSE-214 cells, D. polystachya (DP) induced the highest IL-8 expression (207-fold), followed by Chenopodium album (CA) (194-fold IL-8, 49-fold TNF-α) and CTR (245-fold RIPK2), activating NF-κB, MAPK, and NOD-like receptor pathways critical for teleost immunity. Lonicera japonica (LJ) suppressed TNF-α (0.4-fold) and IRF1 (0.3-fold), indicating anti-inflammatory potential, while S. virgaurea subsp. gigantea (SV) showed biphasic TNF-α modulation (79-fold at 10 μg/mL, 5-fold at 100 μg/mL). These diverse bioactivities, particularly the robust immunomodulatory effects, highlight the promise of these extracts as natural therapeutic agents for fish health management in aquaculture. Full article

Understanding microbial adaptation and tolerance based on the cellular concentration and biosorption capacity provides critical insights for evaluating microbial performance under heavy metal stress, which is essential for selecting efficient strains or consortia for bioremediation applications. In this study, the adaptation and tolerance of Bacillus megaterium and Rhodotorula mucilaginosa to elevated concentrations of copper (Cu) and manganese (Mn) were investigated by introducing the maximum adaptation concentration (MAC) alongside the maximum tolerable concentration (MTC) and the minimum inhibitory concentration (MIC). A Gaussian model was fitted to the relative growth responses to estimate the MACs, MTCs, and MICs. B. megaterium exhibited MACs of 4.6 ppm Cu and 393.9 ppm Mn, while R. mucilaginosa showed MACs of 59.6 ppm Cu and 64.4 ppm Mn, corresponding to concentrations that stimulated their maximum cell density. A biosorption analysis revealed average capacities of 6.3 ± 5.3 mg Cu/g biomass and 28.6 ± 17.2 mg Mn/g biomass, positively correlated with the MTCs, indicating enhanced metal uptake under sublethal stress. The co-culture assays demonstrated dynamic microbial interactions shaped by the type and concentration of metal, including coexistence, competitive substitution, and dominance by tolerance. These findings support the use of MACs as indicators of growth stimulation and MTCs as thresholds for enhanced metal uptake, providing a dual-parameter framework for selecting metallotolerant microorganisms for metal recovery strategies. Full article

With 80% of bacterial infections occurring as biofilms, biofilm-related infections have evolved into a critical public health concern. Probiotics such as Bacillus licheniformis have emerged as promising alternatives, offering new avenues for effective treatment. This study aimed to evaluate the activity of licheniformis against the growth, biofilm formation, motility, and quorum sensing (QS) of Salmonella typhimurium. Several experiments were conducted: The minimum inhibitory concentration (MIC) of Bacillus licheniformis against Salmonella typhimurium was determined to be 0.5 mg/mL using the broth microdilution method. The inhibition zone of 100 mg/mL of B. licheniformis against Salmonella typhimurium was 19.98 ± 1.38 mm; the time-growth curve showed that B. licheniformis can effectively inhibit the growth of Salmonella typhimurium. In biofilm experiments, at the MIC of B. licheniformis, the inhibition rate of immature biofilm of Salmonella typhimurium was 86.9%, and it significantly reduced the production of biofilm components (EPS, e-DNA, and extracellular proteases) (p < 0.05). The disruption rate of mature biofilm by B. licheniformis at the MIC was 66.89%, and it significantly decreased the levels of biofilm components (EPS and e-DNA) (p < 0.5). Microscopic observation showed that both the MIC and 1/2 MIC of B. licheniformis could reduce the number of bacteria in the Salmonella typhimurium biofilm, which was not conducive to the formation and maintenance of the biofilm structure. Swimming/Swarming assays and QS experiments confirmed that B. licheniformis inhibits the motility of Salmonella typhimurium and the secretion of AI-1-type quorum sensing molecules and downregulates the AI-2 quorum sensing system by upregulating lsr gene expression. These findings suggest that B. licheniformis could be a potential antimicrobial agent and biofilm inhibitor. Full article

The envelope stress response in Escherichia coli is primarily governed by the sigma factor RpoE (σ^E), which activates protective genes upon membrane perturbation. Under non-stress conditions, σ^E is sequestered by its anti-sigma factor RseA. In this study, we identify an unexpected role for the nitric-oxide-sensing repressor NsrR in dampening σ^E activity and repressing σ^E-dependent small RNAs, including rybB, micA, and micL. Overexpression of nsrR represses transcription from σ^E-dependent promoters and phenocopies σ^E inactivation, resulting in filamentous morphology and growth defects. Conversely, ΔnsrR de-represses σ^E targets, with additive effects in rseA mutants—supporting an RseA-independent regulatory role. Time-course analysis shows NsrR represses σ^E activity, with kinetics comparable to those of RseA. While in vitro assays failed to detect robust NsrR binding to σ^E target promoters, NsrR directly interacts with σ^E in bacterial two-hybrid assays. Structural modeling using AlphaFold3 supports a plausible NsrR–RpoE interaction interface. These findings suggest that NsrR functions as a noncanonical anti-sigma-like modulator of σ^E, integrating redox and envelope stress signals to maintain membrane homeostasis. Full article

Background: Burkholderia pseudomallei, the causative agent of melioidosis, is intrinsically resistant to multiple antibiotics, posing substantial challenges for treatment. Reports of acquired resistance are increasing, underscoring the need for global surveillance. Objective: This systematic review and meta-analysis aimed to determine the global prevalence of antibiotic-resistant B. pseudomallei isolated from human clinical cases, with a focus on regional differences and variations in antimicrobial susceptibility testing methods. Methods: We systematically searched PubMed, Scopus, and Embase for studies reporting resistance in clinical B. pseudomallei isolates, following PRISMA guidelines. Pooled resistance rates to 11 antibiotics were calculated using a random-effect model. Subgroup analyses were performed based on geographical region and testing methodology (MIC vs. disk diffusion). Results: Twelve studies comprising 10,391 isolates were included. Resistance rates varied across antibiotics, with the highest pooled resistance observed for tigecycline (46.3%) and ciprofloxacin (38.3%). Ceftazidime (CAZ) and trimethoprim–sulfamethoxazole (SXT), commonly used first-line agents, showed resistance rates of 5.3% and 4.2%, respectively. Subgroup analyses of CAZ and SXT revealed significantly higher resistance in studies from Asia compared to Australia and America (p value < 0.0001). Disk diffusion methods tended to overestimate resistance compared to MIC-based approaches, which revealed non-significant differences for CAZ (p value = 0.5343) but significant differences for SXT (p value < 0.0001). Conclusions: Antibiotic resistance in B. pseudomallei exhibits regional variation and is influenced by the susceptibility testing method used. Surveillance programs and standardized antimicrobial susceptibility testing protocols are essential to guide effective treatment strategies and ensure accurate resistance reporting. Full article

Objectives: To investigate epidemiological/drug-resistance characteristics and identify potential factors related to drug-resistant and clustered tuberculosis in Sichuan. Methods: A total of 295 Mycobacterium tuberculosis (MTB) isolates were collected from surveillance sites in Sichuan from 2019 to 2021. The minimum inhibitory concentrations (MICs) of 12 anti-TB drugs were acquired using the broth microdilution method, followed by whole-genome sequencing (WGS) analysis. Results: Of 268 MTB isolates with both WGS and drug-susceptibility testing (DST) results, 159 (59.3%, 159/268) strains belonged to the Beijing lineage (L2). Isoniazid had the highest resistance rate (15.3%, 41/268), followed by rifampicin (9.3%, 25/268). The sensitivity of WGS to predict drug resistance varied from 75% to 97.6%, and the specificity was above 96.0% for all. rpoB Ser450Leu (41.7%, 10/24) and katG Ser315Thr (70%, 28/40) were the most frequent mutations in rifampicin and isoniazid resistance isolates, respectively. The clustering rate in Sichuan was 9.3% (25/268), and patients ≤ 24 years old (aOR = 11.697; 95% CI: 0.817–167.463) had a greater risk of clustering. Conclusions: Our findings prove that WGS is a promising tool for predicting drug resistance to isoniazid, rifampicin, ethambutol, moxifloxacin and levofloxacin in Sichuan. The higher resistance rate to isoniazid emphasizes the urgent need for susceptibility testing surveillance and application management. Improving the diagnosis, treatment and management of patients ≤ 24 years old may reduce the transmission of MTB in Sichuan. Full article

Background/Objectives: Cryptococcosis, caused by Cryptococcus neoformans and Cryptococcus gattii species complexes, remains a significant health concern, particularly among immunocompromised patients. The emergence of antifungal resistance and toxicity of conventional treatment underscore the urgent need for novel therapeutic approaches. Combination therapies represent a promising strategy to enhance efficacy and overcome resistance. This study investigated the antifungal activity of five naphthoquinones against nine isolates of Cryptococcus spp. and assessed their synergistic effects with amphotericin B (AmB). Methods: In this study, five selected naphthoquinones were evaluated for their antifungal activity against Cryptococcus spp. isolates using broth microdilution assays to determine minimum inhibitory concentrations (MICs), according to CLSI guidelines. The potential synergistic effect with AmB was assessed using checkerboard assays, with synergy interpreted based on the fractional inhibitory concentration index (FICI). Cytotoxicity was evaluated in MRC-5 human lung fibroblast cells using the MTT assay. Results: Among the compounds tested, 2-methoxynaphthalene-1,4-dione (2-MNQ) demonstrated antifungal activity, with MIC values ranging from 3.12 to 12.5 µg/mL. Checkerboard assays revealed a synergistic interaction between 2-MNQ and AmB, with a fractional inhibitory concentration index (FICI) of 0.27. The combination reduced the MIC of AmB by 4.17-fold. These findings highlight the potential of synthetic naphthoquinones, particularly 2-MNQ, as effective antifungal agents with synergistic properties when combined with AmB. The observed synergy suggests complementary mechanisms, including increased fungal membrane permeability and oxidative stress induction. Conclusions: This study highlights the potential of 2-MNQ and 2,3-DBNQ as antifungal candidates against Cryptococcus spp., with emphasis on the synergistic interaction observed between 2-MNQ and amphotericin B. The findings reinforce the importance of structural modifications in naphthoquinones to enhance antifungal activity and support the need for further preclinical studies investigating combination therapies aimed at improving treatment efficacy in patients with cryptococcosis. Full article

The emergence of methicillin-resistant Staphylococcus aureus (MRSA) and its biofilm-forming ability underscore the limitations of current antibiotics. In this study, a new compound named tripterhyponoid A was found to effectively combat MRSA, with an MIC of 2.0 μg/mL. It inhibited biofilm formation by downregulating genes related to the quorum sensing (QS) pathway (sarA, agrA, agrB, agrC, agrD, and hld) and eradicated mature biofilms. Furthermore, it induced DNA damage by binding to bacterial DNA, enhancing its efficiency against MRSA. Therefore, its anti-MRSA properties with multiple mechanisms of action make it less prone to developing resistance over 20 days. In addition, it reduced the bacterial load and regulated the levels of inflammatory cytokines IL-6 and IL-10 at the wound site in a mouse skin infection model. This paper provides the first in-depth investigation of the mechanisms of triterpenoids against MRSA by inhibiting the expression of QS system genes and binding to DNA. Full article