Methicillin-Resistant Staphylococcus aureus T144: A Hypervirulent Model Strain for Infection Models

<b>Background/Objectives</b>: Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) presents a major public health challenge due to its multidrug resistance and high virulence. Developing representative model strains is crucial for systematically assessing pathogenesis and antimicrobial therapies. <b>Methods</b>: The highly virulent MRSA strain T144, isolated from pigs, was characterized through whole-genome sequencing and antimicrobial susceptibility testing. Infection models were successfully established in <i>Galleria mellonella</i> and mice to evaluate virulence. A mouse lung infection model was specifically developed to assess bacterial load dynamics, immune responses, and the efficacy of vancomycin treatment. <b>Results</b>: MRSA T144 demonstrated broad-spectrum antibiotic resistance and high mortality rates in both <i>Galleria mellonella</i> and mouse models. Whole-genome sequencing identified multiple virulence-associated genes, including hemolysins and enterotoxins. The concentration of 7 × 10⁸ CFUs was optimized for establishing the mouse lung infection model. In the mouse lung infection model, MRSA T144 demonstrated rapid bacterial proliferation within the first 24 h, followed by a slower growth rate. Significant changes in immune markers were observed, with elevated levels of pro-inflammatory cytokines (IL-1β, IL-6, IL-8, IL-17a, TNF-α) and decreased IL-10 levels. Vancomycin treatment significantly improved survival rates and reduced bacterial load, confirming the model's utility for antimicrobial efficacy studies. <b>Conclusions</b>: The successful establishment of MRSA T144 infection models provides a robust platform for investigating bacterial dynamics, immune responses, and antimicrobial efficacy against highly virulent MRSA strains. These findings highlight the potential of MRSA T144 as a valuable model for developing novel therapeutic strategies.