Nanonized tetracycline cures deadly diarrheal disease ‘shigellosis’ in mice, caused by multidrug-resistant Shigella flexneri 2a bacterial infection

Abstract

We reported earlier about nano-formulation of tetracycline through its entrapment within calcium-phosphate nano-particle (CPNP) and about killing of pathogenic bacterium Shigella flexnari 2a, resistant to tetracycline (and 9 other antibiotics), by the nanonized antibiotic (Tet-CPNP). Here, we report on therapeutic role of Tet-CPNP against deadly diarrheal disease ‘shigellosis’ in mice, caused by Shigella infection. Our findings revealed that occurrence of mushy-stool excretion, colon-length shortening, weight-loss and bacterial colonization in gastrointestinal tract of mice due to shigellosis was significantly reduced by Tet-CPNP treatment. Histo- and immuno-logical studies showed that changes in morphology and level of inflammatory cytokines TNF-α, IL-1β and IFN-γ in intestinal tissue of Shigella-infected mice were reverted to almost normal features by Tet-CPNP treatment. Bulk tetracycline had no anti-shigellosis action. Thus, nanonization of tetracycline rejuvenated the old, cheap, broad-spectrum antibiotic from obsolescence (due to resistance generation), making it highly beneficial for diarrhea-prone developing countries with limited health-care budgets.