Organosulfur compounds as dual-action agents: a critical review of antimicrobial and immunomodulatory potentials, and translational barriers

Abstract

The rise of antimicrobial resistance (AMR) demands therapeutic innovations that not only kill pathogens but also disarm their virulence and bolster host defenses. Organosulfur compounds (OSCs), with their unique integration of antimicrobial and immunomodulatory properties, offer a promising solution. Organosulfur compounds (OSCs) are emerging as dual-action candidates with antimicrobial and immunomodulatory potential, yet their translational readiness remains uneven across subclasses. This critical review synthesizes evidence published between 2010 and 2025 identified through targeted searches of PubMed Central, ProQuest, MDPI, ScienceDirect, and ClinicalTrials.gov , focusing on mechanistic, pharmacokinetic, and One Health–relevant dimensions. OSCs exert antimicrobial effects through thiol-reactive redox disruption, quorum-sensing inhibition, and suppression of virulence-associated transcriptional networks, with several agents demonstrating low-micromolar activity in vitro and measurable biofilm attenuation in preclinical models. Immunomodulatory actions—including Nrf2 activation and NF-κB suppression—are most consistently reported for isothiocyanates such as sulforaphane, which also possesses the strongest human pharmacokinetic dataset (peak plasma conjugate concentrations typically 0.one to two μM; urinary excretion >70% within 24 h). In contrast, thiosulfinates like allicin exhibit potent in vitro activity but are chemically unstable and seldom detectable in vivo , limiting systemic applicability without targeted delivery. Comparative assessment highlights significant evidence gaps: (i) absence of validated pharmacodynamic biomarkers for most OSC subclasses; (ii) limited structural optimization to mitigate off-target thiol reactivity; (iii) lack of controlled clinical trials evaluating infection-related outcomes; and (iv) scarce environmental fate data relevant to One Health frameworks. Together, these gaps underscore that OSCs should not be positioned as near-term therapeutic agents but as mechanistically rich leads requiring stabilization, standardized formulations, and biomarker-driven early-phase studies. This review provides a roadmap for advancing OSCs toward evidence-based antimicrobial and immunoregulatory interventions.