Search Results (1,476)

Background: the primary challenge with implant infections is the formation of biofilm, which harbors dormant bacteria that reduce the effectiveness of antibiotics and amplify antibiotic resistance, exacerbating the global antimicrobial resistance crisis. A potential novel treatment strategy is radioimmunotherapy, which uses antibodies linked to radioisotopes to deliver targeted radiation to the bacteria and biofilm. We describe the first in vivo use of targeted radiation therapy, employing Actinium-225 (α-radiation) and Lutetium-177 (β-radiation) labeled antibodies to treat a Staphylococcus aureus biofilm-associated intramedullary implant infection. Untargeted radiation in the form of unbound radionuclide treatment was also evaluated. Methods: to assess therapeutic efficacy, bacterial counts were performed on implant and surrounding bone after seven days of follow-up. Biodistribution was evaluated using SPECT/CT and ex vivo gamma counting. Results: radioimmunotherapy using an antibody against wall teichoic acid which was labeled with Actinium-225 and Lutetium-177 achieved bacterial reductions between 45% and 93% on the implant and surrounding bone. Surprisingly, a similar antimicrobial effect was observed with unbound Actinium-225 treatment reducing the bacterial load by 80% on the implant and 98% in the surrounding bone. Indications of maximum tolerated dose (MTD) with Lutetium-177 labeled antibodies were observed through hepatic and renal function evaluations. Conclusions: These results should be interpreted in the context of the study’s constraints, particularly the limited animal sample size. Nonetheless, the results suggest that in vivo applied radiation may help reduce a biofilm-associated infection at the implant site as well as in the surrounding bone. These findings encourage further investigation into the use of targeted and non-targeted radiation, potentially combined with antibiotics, to develop effective strategies for eradicating biofilm-associated implant infections. Full article

Ensuring optimal food hygiene is essential for food safety and preventing foodborne illness, although the importance of food hygiene is often overlooked in the household kitchen setting. Adequate, good hygiene practices in the domestic environment are equally important as their implementation in any other food preparation environment, like in the food industry. The current review encompasses research data on the prevalence and isolation of major foodborne pathogenic bacteria (Campylobacter, Salmonella, Listeria monocytogenes, Staphylococcus aureus, Escherichia coli pathotypes, and Clostridium perfringens) from household kitchen equipment, as well as food cleaning utensils used in the kitchen, such as sponges, brushes, dishcloths, and hand towels. The most common bacterial pathogen present in the domestic environment is S. aureus. The latter can be transmitted orally, either via direct hand contact with contaminated kitchen surfaces and/or cleaning utensils, or indirectly through the consumption of contaminated food due to cross-contamination during food preparation (e.g., portioning prepared meat on the same cutting board surface and with the same knife previously used to cut fresh leafy vegetables). Moreover, research findings on the hygiene of food cleaning utensils demonstrate that (i) sponges have the highest microbial load compared to all other cleaning utensils, (ii) brushes are less contaminated and more hygienic than sponges, thus safer for cleaning cutlery and kitchen utensils, and (iii) kitchen dishcloths and hand towels positively contribute to cross-contamination since they are frequently used for multiple purposes at the same time (e.g., drying hands and wiping/removing excess moisture from dishes). Finally, the present review clearly addresses the emerging issue of antimicrobial resistance (AMR) in bacterial pathogens and the role of the domestic kitchen environment in AMR dissemination. These issues add complexity to foodborne risk management, linking household practices to broader AMR stewardship initiatives. Full article

Background: Cutaneous wound infections caused by methicillin-resistant Staphylococcus aureus (MRSA) pose serious threats to public health. Nitric oxide (NO), an endogenous gaseous molecule with antibacterial and wound-healing properties, is a promising next-generation antimicrobial agent with a minimal risk of resistance. However, conventional S-nitrosoglutathione (GSNO)-loaded formulations suffer from GSNO leakage, which could compromise the treatment effect or induce systemic side effects. Although conjugation strategies have been introduced to mitigate this issue, there is still a lack of GSNO-conjugated systems that simultaneously achieve high NO loading and sustained NO release while avoiding harsh external stimuli and complex multistep synthetic processes. Objectives: This research aims to develop a high NO-loading system produced through a simple synthetic process that provides sustained NO release without harsh external stimuli while preventing GSNO leakage for effective treatment of MRSA-infected wounds. Methods: We developed cellulose-based GSNO conjugates via a simple EDC/NHS-mediated covalent coupling to TEMPO-oxidized nanocellulose (NC-GSNO). Results: The NC-GSNO hydrogel achieved high NO loading, minimal leakage, and sustained NO release for more than three days. This controlled NO delivery promoted enhanced wound healing in MRSA-infected models. Conclusions: These findings demonstrate that the NC-GSNO hydrogel is a promising platform for controlled NO delivery and the effective treatment of MRSA-infected wounds. Full article

Background: Antibiotic-loaded bone cement (ALBC) is widely used for local antibiotic delivery in joint arthroplasty to prevent and treat prosthetic joint infections (PJIs). In this study, we evaluated the efficacy of cemented Kirschner (K)-wires coated with various ALBC formulations using a Galleria mellonella infection model against multidrug-resistant (MDR) Staphylococcus aureus and Enterococcus faecalis. Methods: We tested commercially available bone cements, including gentamicin-only formulations (PALACOS R+G) and dual-antibiotic formulations, combining gentamicin with either clindamycin (COPAL G+C) or vancomycin (COPAL G+V), alongside an antibiotic-free control (PALACOS R). In vitro assays—including minimum inhibitory/bactericidal concentration (MIC/MBC) determination, antibiotic release kinetics, agar diffusion, and antibiofilm evaluations—demonstrated effective antibiotic release and significant antimicrobial activity against both planktonic and biofilm-associated bacteria. Results: In vivo, ALBC-coated K-wires were well tolerated in G. mellonella and significantly protected the larvae from S. aureus infection compared to controls. Notably, dual-antibiotic formulations provided superior protection, correlating with substantial reductions in bacterial colonisation on implant surfaces and in surrounding tissues. Conclusions: These findings support the utility of the G. mellonella model as a high-throughput, cost-effective platform for the preclinical evaluation of antimicrobial strategies to prevent and treat PJIs and further demonstrate the effectiveness of dual-loaded ALBC against multidrug-resistant bacteria. Full article

Managing bacterial infections and the spread of microbial resistance is one of the most critical and complex tasks of modern healthcare infrastructures. Antiseptics and disinfectants such as biocides play a significant role in controlling microbial resistance by reducing the microbial load on surfaces, skin, and environments, thereby limiting the opportunity for pathogens to proliferate and develop resistance. Herein, we tested the different interactions of quaternary ammonium compound (QAC)-based biocide compositions in pursuit of a better antimicrobial performance. An extensive microbiological analysis was conducted for 12 selected compositions of various combinations of mono-QACs, bis-QACs, and alcohols on 17 strains of bacteria of the ESKAPEE group and fungi, including 11 clinical highly resistant varieties, highlighting synergistic or additive dynamics. The evaluation showed noticeable improvements in activity, with up to 16-fold MBC and 32-fold MBEC reductions for alcohol-based compositions of lead QAC. Moreover, synergistic interactions were detected and confirmed via an optimized checkerboard assay for pyridinium QAC combinations against planktonic Gram-positive S. aureus with a fractional inhibitory concentration index (FICI) and fractional bactericidal concentration index (FBCI) of 0.39–0.5 and Gram-negative A. baumannii biofilms. The studied biocides demonstrated the long-term preservation of antimicrobial efficiency without resistance development during a 40-day period and do not induce QAC-associated cross-resistance for four commercially available antibiotics with similar mechanisms of action. Full article

Staphylococcus aureus is an important pathogen that can cause widespread infections as well as severe outbreaks of food poisoning. Recent studies have drawn attention to foodborne pathogens such as S. aureus endowed with the ability to form biofilms and increase resistance to antimicrobial agents as well as environmental stress, posing challenges to food safety. The Clp (caseinolytic protease) protein complex plays a crucial role in energy-dependent protein hydrolysis processes. This mechanism is a common way to maintain intracellular homeostasis and regulation in both prokaryotic and eukaryotic cells, especially under stress conditions. In S. aureus, multiple genes encoding Clp ATPase homologues have been identified: clpC, clpB, clpY, clpX, and clpL. This study investigated the roles of clpC in stress tolerance and biofilm formation of foodborne S. aureus RMSA24 isolated from raw milk. Our results showed that the deletion of the clpC gene significantly reduced the bacterium’s tolerance to heat, desiccation, hydrogen peroxide, and high osmotic pressure compared to wild type (WT). Furthermore, the clpC knockout mutant also exhibited a marked decrease in biofilm formation using Crystal Violet Staining (CVS) and Scanning Electron Microscopy (SEM). Finally, compared to WT, there was a total of 102 DEGs (differentially expressed genes), with a significant downregulation of genes related to biofilm formation (isaA and spa) and heat-shock response (clpP and danJ). These findings suggest that clpC regulates environmental tolerance in S. aureus by modulating the expression of stress- and biofilm-related genes, positioning it as a potential biomarker and a novel target for controlling contamination in the food industry. Full article

Human infections caused by pathogenic bacteria remain a major global health concern. Among them, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, and Salmonella typhi are particularly prevalent and associated with significant morbidity and mortality. While antibiotics have long been the cornerstone of bacterial infection treatment, the widespread and often inappropriate use of these drugs has led to the emergence of multidrug-resistant (MDR) strains. This escalating resistance crisis underscores the urgent need for alternative therapeutic strategies. Amid the escalating global antimicrobial-resistance crisis, a genome-wide screen of 1800 Saccharomyces cerevisiae knockouts identified a TAD1-deficient mutant whose cell-free supernatant (CFS) rapidly eradicates multidrug-resistant E. coli, S. aureus, K. pneumoniae, and S. typhi in vitro. CFS disrupts pathogenic biofilms, downregulates biofilm-associated genes, and exerts bactericidal activity by triggering intracellular reactive oxygen species (ROS) accumulation and compromising envelope integrity. Probiotic profiling revealed robust tolerance to an acidic pH and physiological bile, high auto-aggregation, and efficient co-aggregation with target pathogens. In both Galleria mellonella and murine infectious models, administration of CFS or live yeast significantly increased survival, attenuated intestinal histopathology, and reduced inflammatory infiltration. These data establish the TAD1-knockout strain and its secreted metabolites as dual-function antimicrobial-probiotic entities, offering a sustainable therapeutic alternative to conventional antibiotics against multidrug-resistant bacterial infections. Full article

The emergence of multidrug-resistant Staphylococcus aureus underscores the urgent need for novel therapeutic agents targeting essential bacterial pathways. The lipoteichoic acid synthase (LtaS) is crucial for the synthesis of lipoteichoic acid in the cell wall of Gram-positive bacteria and represents a promising and vulnerable target for antimicrobial drug development. This study employed a comprehensive computational pipeline to identify potent inhibitors of the LtaS enzyme. A library of natural compounds was retrieved from the COCONUT database and screened against the crystal structure of the extracellular domain of LtaS (eLtaS) (PDB ID: 2W5R, obtained from the Protein Data Bank) through a multi-stage molecular docking strategy. This process started with High-Throughput Virtual Screening (HTVS), followed by Standard Precision (SP) docking, and culminated in Extra Precision (XP) docking to refine the selection of hits. The top-ranking compounds from XP docking were subsequently subjected to MM-GBSA binding free energy calculations for further filtration. The stability and dynamic behavior of the resulting candidate complexes were then evaluated using 100 ns molecular dynamics (MD) simulations, which confirmed the structural integrity and binding stability of the ligands. Density Functional Theory calculations revealed that screened ligands exhibit improved electronic stabilization and charge-transfer characteristics compared to a reference compound, suggesting enhanced reactivity and stability relevant for hit identification. Finally, ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) profiling was conducted to assess the drug-likeness and pharmacokinetic safety of the lead compounds. These findings support them as promising orally active leads for further optimization. Our integrated approach shortlisted eight initial hits (A–H) that showed interesting scaffold diversity and finally identified two compounds, herein referred to as Compound A and Compound B, which demonstrated stable binding, favorable free energy, and an acceptable Absorption, Distribution, Metabolism, and Excretion, and Toxicity (ADMET) profile. These candidates emerge as promising starting points for developing novel anti-staphylococcal agents targeting the LtaS enzyme that cand be further proved by experimental validation. Full article

Linezolid (LZD) is an oxazolidinone antibiotic effective in the treatment of infection with Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). The decline in susceptibility to linezolid is a concern for antimicrobial chemotherapy. In this study, the prevalence of the LZD minimum inhibitory concentration (MIC) of 2 mg/L (LZD-MIC2), which represents a slightly high value within a range of susceptibility for S. aureus (≤4 mg/L), was investigated retrospectively for staphylococcal species from different sources. We collected the records of LZD MIC of Staphylococcus/Mammaliicoccus that had been obtained in our previous studies on isolates from patients, healthy individuals, and foodstuff. Prevalence of isolates showing LZD-MIC2 was analyzed depending on the type of staphylococcal species and S. aureus clones. In clinical isolates, methicillin-susceptible S. aureus (MSSA) and S. argenteus showed significantly higher LZD-MIC2 rates (20.0% and 21.5%, respectively) than MRSA (7.3%). Among clinical and colonizing isolates of MSSA, LZD-MIC2 was more commonly found in CC1 (ST188, ST2990, etc.), CC8, CC15, ST30, ST97, and ST121 than other lineages. In S. argenteus isolates, which were mostly methicillin-susceptible, there was no significant difference in the LZD-MIC2 prevalence among the three genotypes. The LZD-MIC2 was detected in 18.3% of coagulase-negative staphylococci (CoNS), with S. saprophyticus, S. pasteuri, and M. sciuri showing higher prevalence (30–57%) than other species. The present study revealed that the prevalence of the LZD-MIC2 is different depending on staphylococcal species/types, as they are more common in specific MSSA lineages and some CoNS species. Full article

Antimicrobial resistance (AMR) is a global health threat, increasing morbidity, mortality, and healthcare costs. Multi-drug resistant ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter cloacae) cause most hospital-acquired infections. Local data on their resistance profiles remain limited in low-income settings. This study assessed the prevalence and resistance patterns of ESKAPE pathogens isolated from clinical specimens at Rwanda Military Referral and Teaching Hospital. A descriptive cross-sectional study was conducted from June 2022 to January 2023. ESKAPE isolates were identified and tested for antimicrobial susceptibility using the BD Phoenix M50 System. Data on sample type, ward, and demographics were analyzed. Of 744 bacterial findings, 207 (30%) were ESKAPE isolates. After excluding duplicates and non-recovered isolates, 156 were identified as ESKAPE. K. pneumoniae was most common (41%), followed by S. aureus (27%), A. baumannii (13%), P. aeruginosa (11%), and E. cloacae (8%); no E. faecium was detected. Among Gram-negatives, 63% were resistant to third-generation cephalosporins and 32% to carbapenems, with A. baumannii showing highest resistance (85% and 75%). Methicillin-Resistance in Staphylococcus aureus (MRSA) was 7%. This first hospital-based study in Rwanda shows high cephalosporin and carbapenem resistance, highlighting the need to strengthen diagnostics and stewardship. Full article

Milk is an important agricultural product and is consumed worldwide. However, the dairy sector faces a significant challenge due to bovine mastitis, a common disease that has a substantial impact on the dairy industry. In more severe cases, it leads to the culling of chronically infected cows. Mastitis poses a risk due to the frequent use of antibiotics in treatment, which contributes to the spread of bacteria with antimicrobial resistance. The present study aimed to evaluate the antimicrobial and antibiofilm potential of a pyroligneous extract of Eucalyptus urograndis (clone I144) against multidrug-resistant Staphylococcus aureus, the causative agent of mastitis. Sensitivity profiles to various conventional antibiotics were assessed, including the minimum inhibitory concentration (MIC), the minimum bactericidal concentration (MBC), and biofilm inhibition, in ten Staphylococcus aureus strains using the crystal violet method. The results showed that the multidrug-resistant strains were sensitive to the pyroligneous extract of Eucalyptus urograndis (clone I144) at a concentration of 12.5% and exhibited antibiofilm activity starting at a concentration of 3.13%. In conclusion, our findings show that the pyroligneous extract of Eucalyptus urograndis (clone I144), at 12.5%, inhibited different multidrug-resistant S. aureus and MRSA strains isolated from bovine mastitis. These results indicate that the extract represents an effective preventive strategy against mastitis-causing pathogens that are difficult to treat, making it a promising alternative to reduce the dependence on synthetic antibiotics. In vivo studies are needed to confirm these findings and provide a basis for evidence-based clinical guidelines. Full article

Introduction: Globally, microbial infections are projected to be among the leading causes of death by 2050 due to rising drug resistance. Antimicrobials are vital for treating both animals and humans worldwide. However, their overuse and misuse accelerate drug resistance, posing a serious threat to public health. Coumarin is a naturally occurring compound contributing health-beneficial features in drug discovery. Its high solubility in organic solvents, high bioavailability, simple structure, low toxicity, and low molecular weight make it an ideal candidate for combining with other pharmacophores to develop new therapeutic agents. This compound exhibits several biological activities, including antimicrobial, anticancer, anti-inflammatory, antidiabetic, neuroprotective, and anticoagulant effects, motivating medicinal researchers to hybridize it with other compounds to enhance its pharmacological efficacy. Hybridization of different pharmacophores via suitable linkers, including cleavable and non-cleavable ones, is a promising approach in drug development, resulting in new therapeutics with improved biological activity. Therefore, the hybridization of coumarin with other pharmacophores has become an interesting paradigm for medicinal scientists. Aim: This review aims to summarize the existing scientific literature on coumarin-based hybrid compounds with antimicrobial capabilities and discuss the structure–activity relationship (SAR) of these hybrids to potentially guide future research on and development of coumarin-based drugs for microbial treatment. Material and Methods: The review focuses on open-access literature about coumarin hybrid drugs available through searching tools such as Google, Google Scholar, ScienceDirect, and Scopus, published from 2024 to 2025. Results: Coumarin hybrids exhibit promising antimicrobial activity, particularly against S. aureus and C. albicans. The SAR reveals that halogenation, bulky aromatics, nitro, and hydroxyl groups enhance the interaction of the coumarin rings with amino acid residues. Conclusions: The reported coumarin hybrids showed a promising antimicrobial activity, with structural modifications influencing their activity. Hence, more studies, including more pre-clinical and clinical evaluations, are recommended for these hybrid compounds. Full article

Staphylococcus aureus is a common foodborne pathogen, posing significant concern due to the emergence of its multidrug-resistant (MDR) strains. The aim of this study was to assess the antibiotic resistance profiles in S. aureus isolated from raw poultry, the associated resistance genes, and their ability to form biofilms. S. aureus was isolated and identified using conventional microbiological methods. Antimicrobial susceptibility profiles were assessed using the disk diffusion method, and biofilm-forming ability was evaluated using the microtiter plate assay. The presence of antimicrobial resistance genes was determined by PCR. A total of 45 isolates were isolated. High resistance rates were observed against penicillin (88.9%), tetracycline (86.7%) and doxycycline (66.7%). Of the isolates, 71.1% were classified as multidrug-resistant (MDR) organisms, and 60% exhibited a multiple antibiotic resistance index greater than 0.2. PCR analysis revealed the presence of the resistance genes blaZ (86.7%), mecA (27.3%), tet(M) (46.2%), tet(K) (35.9%), tet(S) (59%), erm(B) (51.9%), and erm(C) (59.3%). A total of 44 isolates were biofilm producers: 46.7% were weak producers, 46.7% were moderate producers, and 4.4% were strong producers. These findings highlight a significant public health concern, emphasizing the need for stringent hygiene practices and continuous monitoring to limit the spread of resistant pathogens through the food chain. Full article

This study evaluated the microbiological quality, presence of virulence genes, and antimicrobial resistance of Staphylococcus aureus and Escherichia coli in sheep and goat milk and traditional Romanian dairy products (Telemea and Burduf cheeses). Raw milk contained high levels of coagulase-positive staphylococci (CPS; 5.2 log CFU/mL) and E. coli (4.3 log CFU/mL), with several samples exceeding legal limits. Sour cream exhibited moderate CPS (1.2–1.9 log CFU/g) and E. coli (0.4–3.12 log CFU/g) counts, with occasional non-compliance. Cheeses had low CPS (0.52–0.84 log CFU/g) and E. coli (0.37–0.89 log CFU/g) levels, all within permissible limits. Molecular analysis detected the nuc gene in 21 sheep milk samples, of which 85.7% also carried the sea gene and 14.3% carried seb. Additionally, two goat milk samples tested positive for both nuc and sea. Three Telemea cheese samples were also sea-positive. Among raw milk samples, 10 E. coli isolates carried stx1, and two additionally harbored hly, while dairy products were negative for E. coli virulence genes. Antimicrobial susceptibility testing showed high resistance of S. aureus to penicillin (90.5%) and ampicillin (85.7%), with multidrug resistance among sea- and seb-positive isolates. STEC isolates showed resistance to ampicillin (70%), tetracycline (50%), and trimethoprim–sulfamethoxazole (40%), but remained susceptible to amoxicillin–clavulanic acid. Full article

The utilization of agro-byproducts for textile dyeing and finishing is strongly suggested to meet sustainability and cost-efficiency objectives. Despite recently proliferating studies, three major issues hinder the industrialization of such a technique: identifying reasonable bio-resources, ensuring compatibility between agro-byproducts and textile substrates, and achieving satisfactory color depth, functionality, and durability. This research introduces an approach that forms and fixes silver nanoparticles (AgNPs) on silk using three representative flavonoids (FLs)—Quercetin (QUE), Baicalin (BAI), and Rutin (RUT)—through a single-step in situ bio-reduction. Results demonstrate that FLs-synthesized AgNPs@silk generates attractive spectra of hues, varying from pale cream-brown to deep golden-brown. Using an equivalent quantity of FLs, the color intensity of silk descends in QUE-Ag@silk > BAI-Ag@silk > RUR-Ag@silk, due to the decreasing reactivity and binding affinity of FLs to silk. SEM reveals uniformly distributed spherical AgNPs in dimensions between 20 and 40 nm on silk and the dimension inversely correlates with FLs concentration while being directly proportional to silver nitrate. The modified silk exhibits remarkable antimicrobial performance (>98% pathogen elimination) and exceptional wash resistance (>90% reduction both of E. coli and S. aureus after ten cycles of washing). Additionally, the FLs-synthesized AgNPs provide silk with superior UV shielding capability. This study stems from environmental awareness and sustainable production of AgNPs by FLs, ready for developing hygienic and therapeutic textile materials. Full article