S.M. GANORKAR AND H.S. MALPANI
Abstract
Lower respiratory tract infections pose a formidable global health burden due to hyperviscous mucus accumulation, escalating antimicrobial resistance, and the formation of recalcitrant bacterial biofilms. While N-acetylcysteine (NAC) is routinely prescribed in clinical practice as a mucolytic agent, emerging pharmacological evidence demonstrates its multi-target capacity as an antimicrobial and biofilm-disrupting molecule. This review provides a rigorous synthesis of N-acetylcysteineâs mechanisms of action, evaluating its capacity to suppress bacterial adherence, degrade extracellular polymeric substances (EPS), cleave extracellular DNA (eDNA), and interfere with cell-to-cell quorum sensing networks. Specifically, synthesised findings from evaluated in vitro literature demonstrate that 0.5 -1.0 mg/ml of NAC reduces Pseudomonas aeruginosa matrix polysaccharides by up to 44.59% and successfully detaches mature biofilms. Furthermore, 30 mM of NAC achieves over 90% matrix disruption and a 2-to-3 log10 (99% to 99.9%) reduction in Staphylococcus aureus viability via structural eDNA cleavage, while supra-inhibitory concentrations of NAC eradicate up to 81.5% of mature clinical staphylococcal biofilms. Moreover, it investigates how N-acetylcysteine, when used alongside conventional antibiotics, bacteriophages, and traditional respiratory herbs, can boost drug penetration and break down established biofilm structures. Overall, this review underscores N-acetylcysteineâs substantial clinical potential as a multi-target adjunctive therapy for difficult-to-treat infections in combination with traditional medicinal herbs, while stressing the critical need for standardized dosing protocols and in vitro concentration-dependent assays to confirm these encouraging interactions.