Comparative Modeling of Antibiotic Resistance, Tolerance, and Persistence in Mycobacterium tuberculosis and Staphylococcus aureus

Antibiotic resistance, tolerance, and persistence represent key bacterial survival strategies that impact treatment outcomes and global health. While Staphylococcus aureus is a rapidly growing pathogen associated with acute infections, Mycobacterium tuberculosis exhibits slow growth and chronic persistence, necessitating prolonged antibiotic regimens. In this study, we developed mathematical models and computational simulations to compare bacterial survival under antibiotic exposure, quantifying differences in resistance, tolerance, and persistence. Using logistic growth equations and biphasic killing models, we simulated bacterial population dynamics under antibiotic pressure. Our results indicate that S. aureus exhibits rapid initial tolerance with a killing rate of 0.2/hour, followed by a sharp decline, whereas M. tuberculosis displays a prolonged persistence phase with a slow killing rate of 0.001/hour, allowing it to survive extended antibiotic exposure. The transition from fast to slow killing occurs significantly earlier in S. aureus (80 hours). These findings highlight the necessity of prolonged therapy for tuberculosis and suggest that alternative persister-targeting interventions are needed for persistent S. aureus infections.