The meteoric rise of antimicrobial resistance (AMR), marked by decreased antibiotic effectiveness against pathogenic bacteria, has sparked widespread concern. This phenomenon increases potential threats to public health by significantly hampering the clinical use of currently available antimicrobial agents, such as macrolides, β-lactam and glycopeptides antibiotics. Staphylococcus aureus (S. aureus), namely the Methicillin-Resistant Staphylococcus aureus (MRSA), is a common opportunistic pathogen that causes various types of infections and has become one of the top healthcare problems, particularly in low-income countries. In light of bacterial evolution and the unintentional use of antibiotics for medical purposes in communities and hospitals, as well as in agriculture and livestock for non-medical purposes. These events have contributed to the development and spread of antimicrobial resistance. Furthermore, resistant to our most muscular treatments against invasive S. aureus infections, such as vancomycin, is no longer successful due to the emergence of Vancomycin-Resistant S. aureus (VRSA). The scientific community is looking for creative and spectacularly effective strategies to address this global issue in response to this pandemic threat generated by the spread of antimicrobial resistance strains, with the threat of limited treatment choices against S. aureus. In this review, we highlighted the molecular mechanisms of antibiotic resistance and explained the antibiotic resistance profile of Methicillin-resistant S. aureus. On the other hand, we discuss distinguished tactics for manipulating S. aureus resistance mechanisms, such as the discovery of new chemical entities that possess antimicrobial activity with novel mechanisms of action, utilization of combinatorial antibiotic therapies, chemical derivatization and repurposing of existing known drugs to improve their antibacterial efficacy, design novel vaccine for S. aureus, antimicrobial peptides and nanoparticles as a magic bullet, and finally, by implementing the One Health Agenda against S. aureus, this holistic strategy seeks to address the spread of antibiotic resistance across the interrelated health loop of human, animals, and environments.

New nickel(II), palladium(II), and platinum(IV) complexes were synthesized by reacting the metal ions with benzidinedioxime in a 1 : 1 mole ratio. The CHN elemental analysis, spectroscopic analyses, and powder X-ray diffraction (PXRD) results showed that two Ni(II) and two Pd(II) ions coordinated to two benzidinedioxime ligands via the nitrogen atoms of both oxime groups and the two azomethine nitrogen atoms. In the case of the dinuclear platinum(IV) complex, however, each Pt(IV) is coordinated with the two oxygen atoms of the oxime group and the two azomethine nitrogen atoms of the ligand. Both elemental analyses and PXRD indicated that the complex ions of Ni(II) and Pt(IV) have distorted octahedral geometry, whereas Pd(II) has a square planar geometry. Molecular docking studies showed that the nickel(II) complex is the most potent dual DHPS/DHFR bacterial inhibitor. The receptor of the DHPS enzyme (3ZTE) showed the best interaction with the nickel(II) complex when compared to a receptor of the DHFR enzyme (3FRB). All the synthesized complexes and ligand exhibited significant results against PS. Aeruginous than their corresponding SMX–TMP drug. Among the three synthesized complexes, the nickel(II) complex possessed the highest antimicrobial activities against tested microorganisms.

Terminalia brownii Fresen, an African medicinal plant, is known for its analgesic, antiulcer, and antimicrobial properties, with its leaves, bark, and fruits deeply ingrained in indigenous healing practices. Two lectins, TerBLL (from leaves) and TerBSL (from seeds) of Terminalia brownii Fresen, were purified using salting-out and affinity chromatography on a fetuin-agarose column. The purified lectins were then assessed for protein yield, hemagglutination activity, and physicochemical properties. Both TerBLL and TerBSL have subunits with molecular weights of 57.3 and 65.7 kDa, respectively. TerBLL remains stable at 60–80 °C and is activated by Mn⁺², while TerBSL is activated by Zn⁺². These lectins maintain consistent activity under acidic conditions, with TerBLL demonstrating heightened activity at extreme alkaline pH. TerBLL retained 50 % of its activity in 2–8M urea, in contrast to the 13 % of TerBSL. Investigation of the properties of TerBLL revealed that it had antinociceptive effects, reducing abdominal pain and prolonging latency time in the hotplate assay, potentially through μ-opioid receptor blockade akin to that of morphine. TerBLL exhibits antiulcer activity at doses of 0.25 and 1 mg/kg, reducing ulcer formation by up to 33 %, comparable to that of pantoprazole (80 mg/kg). The physiochemical attributes of TerBLL, in addition to its pain-relieving and gastroprotective effects, underscore its therapeutic promise, which is consistent with its traditional use.

Mycobacterium tuberculosis (MTB) remains a deadly infectious agent and a global health challenge, particularly due to the emergence of multidrug-resistant strains. Mycobacterial serine/threonine protein kinase E (PknE) is vital for mycobacterial survival under nitric oxide stress by altering Toll-like receptor expression, suppressing apoptosis, increasing inflammation, and modulating costimulatory molecules. This study employed a structure-based in silico workflow comprising virtual screening of 2,202 FDA-approved compounds, molecular docking, 300 ns molecular dynamics (MD) simulation molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) binding free energy calculations, principal component analysis (PCA), free energy landscape (FEL) analysis, and in silico toxicity profiling, to identify candidate PknE inhibitors. Molecular docking identified netilmicin, dirithromycin, acarbose, and ertapenem as top candidates, with docking scores of − 13.13 to − 15.86 kcal/mol. MD simulations confirmed complex stability with RMSD values near 1 nm, while MM/PBSA analysis revealed favourable binding free energies: netilmicin (− 1.47 ± 0.18), ertapenem (− 11.70 ± 1.22), dirithromycin (− 17.80 ± 0.13), and acarbose (− 18.90 ± 0.06 kcal/mol). PCA-based FEL analysis confirmed thermodynamic stability across all complexes, with DTM–PknE exhibiting the lowest minimum Gibbs free energy (15.7 kJ/mol). In silico toxicity profiling demonstrated acceptable safety profiles for all leads. These findings provide a strong computational basis for repurposing these agents as adjunct anti-TB therapies, pending experimental validation.