Antimicrobial peptides (AMPs) have emerged as promising alternatives to conventional antibiotics, addressing the growing concern of antibiotic resistance. Their efficacy primarily relies on two key properties: amphiphilicity and cationic charge, which promote targeted action on bacterial membranes. The Lynronne family, identified in the bovine rumen through metagenomic screening, already exhibits notable antimicrobial activity and low toxicity, making it a strong candidate for further development [1]. Our goal is to enhance the therapeutic potential of these AMPs using conventional and innovative strategies. Traditional approaches include substitutions with cationic amino acids and D/L enantiomeric modifications.

In parallel, we employed artificial intelligence techniques using the MRL (Molecular Reinforcement Learning) model for AMP design, based on the biophysical properties of the Lynronne family (cationic charge, hydrophobicity). The activity and toxicity of the designed peptides were first evaluated in silico using various prediction tools (MIC predictors and toxicity/hemolysis predictor). Their antimicrobial activity against diverse pathogens and their cytotoxicity on human cells were then measured, allowing comparison between predicted and measured activities. Their mechanism of action was studied via biophysical techniques, membrane permeabilization assays, and molecular dynamics simulations (GROMACS), confirming specific interactions with bacterial membranes and membranolytic effects. This study highlights how combining rational design strategies and AI can optimize Lynronne peptides, reinforcing their potential as alternatives to conventional antibiotics.

The emergence of antibiotic-resistant pathogens has necessitated the exploration of plant-based antimicrobial agents as alternative therapies. This study evaluates the antibacterial activity of Detarium senegalense stem bark extract against clinically significant bacterial species: Staphylococcus aureus, Salmonella species., and Bacillus species. The stem bark was collected from Daura Local Government Area of Katsina state, Nigeria. Clinical isolates were collected from Ahmadu Bello University Medical Centre then taken to Department of Microbiology for reconfirmation using standard microbiological methods. The stem bark was extracted using ethanol, and the antibacterial efficacy was assessed through the agar well diffusion method at concentrations of 100mg/ml, 50mg/ml, 25mg/ml, and 12.5mg/ml. Inhibition zones were recorded to determine the effectiveness of the extract, and the Minimum Inhibitory Concentration (MIC) was established. The extract demonstrated significant antibacterial activity, with notable inhibition zones against S. aureus and Salmonella species at 50mg/ml and 25mg/ml, respectively, indicating its potential as a natural antibacterial agent. Phytochemical analysis revealed the presence of bioactive compounds such as flavonoids, tannins, and alkaloids, which likely contribute to the observed antimicrobial effects. This study supports the potential use of Detarium senegalense stem bark as a source of bioactive compounds against pathogenic bacteria, providing a foundation for future research into its therapeutic applications and possible development as an alternative treatment for bacterial infections.

This review explores the biofilm architecture and drug resistance of Enterococcus faecalis in clinical and environmental settings. The biofilm in E. faecalis is a heterogeneous, three-dimensional, mushroom-like or multilayered structure, characteristically forming diplococci or short chains interspersed with water channels for nutrient exchange and waste removal. Exopolysaccharides, proteins, lipids, and extracellular DNA create a protective matrix. Persister cells within the biofilm contribute to antibiotic resistance and survival. The heterogeneous architecture of the E. faecalis biofilm contains both dense clusters and loosely packed regions that vary in thickness, ranging from 10 to 100 µm, depending on the environmental conditions. The pathogenicity of the E. faecalis biofilm is mediated through complex interactions between genes and virulence factors such as DNA release, cytolysin, pili, secreted antigen A, and microbial surface components that recognize adhesive matrix molecules, often involving a key protein called enterococcal surface protein (Esp). Clinically, it is implicated in a range of nosocomial infections, including urinary tract infections, endocarditis, and surgical wound infections. The biofilm serves as a nidus for bacterial dissemination and as a reservoir for antimicrobial resistance. The effectiveness of first-line antibiotics (ampicillin, vancomycin, and aminoglycosides) is diminished due to reduced penetration, altered metabolism, increased tolerance, and intrinsic and acquired resistance. Alternative strategies for biofilm disruption, such as combination therapy (ampicillin with aminoglycosides), as well as newer approaches, including antimicrobial peptides, quorum-sensing inhibitors, and biofilm-disrupting agents (DNase or dispersin B), are also being explored to improve treatment outcomes. Environmentally, E. faecalis biofilms contribute to contamination in water systems, food production facilities, and healthcare environments. They persist in harsh conditions, facilitating the spread of multidrug-resistant strains and increasing the risk of transmission to humans and animals. Therefore, understanding the biofilm architecture and drug resistance is essential for developing effective strategies to mitigate their clinical and environmental impact.

Antimicrobial-resistance (AMR) is a ‘natural phenomenon’ based on a selection of microorganisms able to survive in an unfavourable environment, owing to genetic mutations or the acquisition of “pre-established” resistance genes. The overuse and misuse of antibiotics can favour the emergence and spread of AMR, with negative impacts on the management of bacterial infections and economic implications for healthcare systems. Research and development of natural antibacterial molecules, which exhibit multiple bio-functionalities and are less likely to induce resistance in bacteria, could represent a priority in the coming years to improve the antibacterial activity of existing molecules and counteract AMR. The present study identified the most effective concentration and contact time of Thymus vulgaris L. essential oil (TEO) to achieve in vitro bactericidal activity against twenty-one bacterial strains isolated from different specimens. In total, 10 μl of a solution containing the TEO and the bacterial strains isolated was sown in Petri-dishes for successive assessments of antibacterial efficacy, in terms of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC), after 24 and 48 hours, respectively. The identified strains (Mammaliicoccus lentus, 2Escherichia coli, Salmonella enterica subsp.enterica sierovar derby, 2Staphylococccus, S.xylosus, S.chromogenes, S.epidermidis, S.enterica subsp.diarizonae, S.enterica subsp.salamae, S.enterica subsp.houtenae, E.coli(b), S.aureus(b), Citrobacter freundii, Enterococcus feciorum, Proteus mirabilis, Acinetobacter cioffi, Pseudomonas putrefaciens and Klebsiella pneumoniae), each with different resistance profiles, and two ATCC strains (S.aureus and Streptococcus mutans) were tested after 6, 12, 24, and 48h of contact with TEO at different concentrations, from 5% to 2.5% to 1.25%(v/v), corresponding to 450, 225, and 112.5g/mL, respectively. We observed a complete inhibition of all bacterial strains after 12h of incubation at all TEO concentrations, demonstrating the efficacy of TEO against several Gram-positive and Gram-negative bacteria with different AMR. Further studies are needed to define the exact molecular mechanisms of TEO and its possible uses.

Introduction: Representatives of the genus Trichosporon are basidiomycetous yeast-like microorganisms that are widely distributed in nature. The genus Trichosporon includes species capable of causing both superficial and invasive infections associated with high mortality rates. A notable characteristic of the Trichosporon species is their resistance to many antifungal agents that are commonly used for the treatment of invasive fungal infections.

Materials and Methods: Trichosporon sp. were isolated from samples of the affected skin of a patient with a chronic infection. Identification was performed using MS (mass spectrometry).

The producer Streptomyces sp. strain SVP-71 was isolated from bentonite samples. The antifungal antibiotic was extracted from the culture fluid and biomass using butanol. Primary purification and metabolite separation were carried out using TLC. The obtained antibiotic was applied to sterile paper discs (14 µg per disc). Specific activity control was performed using discs with dried butanol.

The susceptibility of the clinical isolate to the obtained antibiotic was determined using the DDM, according to CLSI M44 guidelines. Caspofungin discs (5 mg, HiMedia), one of the most effective antifungal antibiotics, were used as a reference.

Results: Screening studies revealed the antagonistic activity of Streptomyces sp. strain SVP-71 against a wide range of yeast-like and filamentous fungi that are pathogenic to humans, including the emerging pathogen Candida auris. The disc diffusion method also confirmed the activity of secondary metabolites from Streptomyces sp. strain SVP-71 against the clinical isolate of Trichosporon sp., with growth inhibition zones reaching up to 20 mm. In contrast, echinocandin antibiotics (caspofungin) showed no specific activity against this microorganism.

Conclusions: The strain Streptomyces sp. SVP-71 demonstrates promise as a source of new antifungal agents, particularly for treating infections caused by fungi with natural resistance to standard antibiotics, such as echinocandins. This is of significant importance in the fight against mycoses that present as severe invasive infections.