In vivo infection in mice demonstrates that antibiotic susceptibility of S. aureus is conversely correlated with prior infection.

(A) Schematic representation. C57BL/6J mice were given subcutaneous (s.c.) primary infection of S. aureus or PBS 18 days prior to secondary S. aureus infection (s.c.). RIF therapy was initiated at 23 d and continued for 3 days. Created by Biorender. (B) Skin disease score of mice at 23 d and 26 d. (C) Skin lesion size of mice was measured at 23 d and 26 d. (D) Bacterial burden in skin abscesses from infected (S. aureus) or uninfected (PBS) mice was determined by CFU enumeration at 23 and 26 d. (E) % Survival of S. aureus cells in mice with different infection histories after rifampicin therapy compared with before rifampicin treatment (extrapolated from D). (F) Representative H&E-stained skin sections at 23 and 26 d (magnification of 100 ×). The black arrow indicates inflammatory cells infiltration. E: epidermis; D: dermis; A: adipose tissue; M: muscle fibres. S. a, S. aureus. Data pooled from 2 independent experiments with 5 to 6 mice per group. *p < 0.05, **p < 0.01, ***p < 0.001, *****p < 0.0001. Two-way ANOVA or student’s t test analysis of variance was performed and the data are presented as the means ± SEM.