Antimicrobials from nano sulfur: Innovations, applications, and future perspectives

The sudden worldwide spread of multidrug-resistant (MDR) Gram-negative bacilli (GNB), particularly carbapenemase producers such as New Delhi metallo-β-lactamase-1 (NDM-1), is an emerging, clinically and public health-relevant challenge. The antibiotics, including carbapenems, become progressively less effective, making it necessary to develop alternative therapeutic options. Nanotechnology opens new avenues, including unique physicochemical properties of nanomaterials at the nanoscale. Sulfur, which has long been recognized for its antimicrobial activity, proves to be more effective when engineered as sulfur nanoparticles (S-NPs). This review emphasizes the antibacterial promise of PEG-stabilized S-NPs against MDR pathogens. PEGylation enhances the stability, dispersibility, and bioavailability of nanoparticles, leading to enhanced antimicrobial efficacy and decreased cytotoxicity in comparison to unaltered S-NPs. Mechanistic investigations indicate that S-NPs affect microbes through reactive oxygen species production, membrane disruption in bacteria, inhibition of metabolic processes, and probable interactions with resistance determinants like NDM-1. Comparative studies demonstrate that PEG-S-NPs have lower minimum inhibitory concentrations than their larger, uncoated counterparts, highlighting the influence of surface engineering on antimicrobial activity. Moreover, synergies with last-line antibiotics such as colistin and tigecycline highlight their potential for combination therapy. In vitro and in vivo evidence validating their broad-spectrum effectiveness and acceptable safety profiles has created challenges in large-scale production, long-term biocompatibility, ecological safety, and translation to regulatory approval. Future studies would emphasize standardized comparison studies, mechanistic explanation, and preclinical assessment to facilitate clinical use. PEGylated S-NPs are a promising next-generation antimicrobial approach that can revolutionize the treatment of MDR infections and solve one of the most important global health issues.