Effect of Antimicrobial Prophylaxis on <i>Corynebacterium bovis</i> Infection and the Skin Microbiome of Immunodeficient Mice

Abstract

<i>Corynebacterium bovis</i> is an opportunistic pathogen of the skin of immunodeficient mice and is sensitive to oral antibiotics that reach therapeutic blood concentrations. However, prophylactic antibiotics are considered to be ineffective at preventing <i>C. bovis</i> infection. In addition, the effect of <i>C. bovis</i> on the skin microbiome (SM) of common immunodeficient mouse strains has yet to be characterized. Consequently, we evaluated whether oral prophylactic antibiotics prevent <i>C. bovis</i> infection after inoculation. An infectious dose of <i>C. bovis</i> was applied to the skin of Hsd:Athymic Nude (nude) and NOD. Cg-<i>Prkdc^{scid Il2rgtm1Wjl}</i>/SzJ (NSG) mice. Mice were then housed individually and assigned randomly to receive either untreated drinking water (<i>Cb</i>+Abx-group) or prophylactic amoxicillin-clavulanic acid in the drinking water (0.375 mg/mL) for 14 d (<i>Cb</i>+Abx+group). A third treatment group of each mouse strain was uninoculated and untreated (<i>Cb</i>-Abx-group). Mice from all groups were serially sampled by using dermal swabs to monitor <i>C. bovis</i> infection via quantitative real-time PCR and the SM via 16S rRNA sequence analysis. Fourteen days of prophylactic antibiotics prevented the perpetuation of <i>C. bovis</i> skin infection in both strains. Only the combination of <i>C. bovis</i> inoculation and oral antibiotics (<i>Cb</i>+Abx+) significantly affected the SM of NSG mice at day 14; this effect resolved by the end of the study (day 70). In mice that did not receive antibiotics, <i>C. bovis</i> significantly altered the SM of nude mice but not NSG mice at days 14 and 70. These findings demonstrate the potential benefit of prophylactic antibiotics for prevention of <i>C. bovis</i> infection. However, indirect effect of antibiotics on commensal bacteria and potential effects on xenograft models must be considered.