Microorganisms

To address the urgent challenge of antimicrobial resistance, a series of twenty novel C-28 modified betulinic acid derivatives was designed and synthesized. Several derivatives, particularly 3b, 3d, 3e, and 3o, displayed notable antibacterial activity against Gram-positive bacteria, including Staphylococcus aureus and vancomycin-resistant Staphylococcus aureus (VRSA). The most active compound, 3d, was subjected to further mechanistic evaluation: it produced concentration-dependent inhibition zones in Oxford cup assays, exhibited bactericidal kinetics in time-kill studies, and significantly suppressed biofilm formation. Molecular docking suggested that the anti-biofilm activity of 3d may be mediated through binding to the staphylococcal accessory regulator A (SarA), a key transcriptional regulator of biofilm formation. The molecular dynamics study provided additional confirmation of the effective binding between 3d and SarA. These results highlight compound 3d as a promising lead for the development of novel anti-biofilm agents targeting drug-resistant Gram-positive infections.

The growing antimicrobial resistance (AMR) is threatening traditional treatments for oral diseases like dental caries and periodontitis, which constitute a significant global health burden. The study aimed to isolate Bacillus species from marine samples, to assess their biosurfactant-producing capabilities, and to evaluate their antibacterial activity against oral pathogens. Bacillus strains were isolated from marine water and sediment samples, identified by phenotypic and genotypic methods, and screened for their biosurfactant-producing ability by drop collapse, hemolytic activity, bacterial adhesion to hydrocarbons (BATH), oil displacement, and emulsification assays. Ethyl acetate extracts of these Bacillus strains were tested for antibacterial efficacy against four oral pathogens (MTCC strains) by the agar-well diffusion method. Among 81 bacterial isolates, 13 were confirmed as Bacillus species by phenotypic and 16S rRNA gene sequencing. Six Bacillus isolates displayed significant antibacterial activity, and the majority were beta-hemolytic. Bacillus strain TVD12 (50 mg/mL) exhibited superior performance by inhibiting S. mutans (31 mm ± 0), S. anginosus (30.5 mm ± 0.7), S. aureus (20 mm ± 1.4), and E. faecalis (29 mm ± 4.24). Bacillus strain TVW12 (500 μg/mL) performs better in antibiofilm activity by inhibiting E. faecalis 90%, S. aureus 87.4%, and S. mutans 76.8%. Statistical analysis revealed a distinct dual-activity profile, characterized by consistent broad-spectrum antimicrobial efficacy (p = 0.809) alongside specialized, pathogen-specific antibiofilm inhibition (p = 0.004). Marine-derived Bacillus strains, such as TVW12, and TVD12 demonstrated effective antibacterial and antibiofilm properties, offering a feasible approach to combat oral pathogens, contributing to sustainable development goals (SDGs) by addressing the challenges of antimicrobial resistance (SDG 3) through sustainable marine bioprospecting (SDG 14). These findings suggest their possibility in developing novel antibacterial agents against oral pathogens in future therapeutic applications.

Cronobacter sakazakii is a formidable foodborne pathogen that poses a severe, often fatal threat to neonates and immunocompromised individuals, with contaminated powdered infant formula as the primary transmission vehicle. Infections can lead to devastating conditions, such as meningitis, necrotizing enterocolitis, and sepsis, with alarmingly high mortality rates. Clinical management is hampered by the lack of standardized treatment guidelines and the emergence of antibiotic resistance. However, ongoing research into its molecular pathogenesis continually covers novel targets for intervention. In this review, we synthesize recent advances in our understanding of the sophisticated mechanisms that enable C. sakazakii to cause disease. We argue that its virulence hinges on a multi-faceted strategy, including efficient host invasion and tissue penetration via outer membrane proteins, sophisticated immune evasion tactics for intracellular survival, a repertoire of regulated virulence determinants, resilient biofilm formation, and robust stress response systems that ensure environmental persistence. As research continues to decipher these intricate host–pathogen interactions, we highlight promising future directions, including the development of rapid on-site diagnostics, the application of effective biocontrol strategies like phage therapy and probiotics, and the formulation of targeted therapeutic regimens. Ultimately, integrating these multifaceted insights is paramount to developing comprehensive strategies for preventing and controlling the global health burden imposed by C. sakazakii.