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bioRxiv · 10.1101/2025.05.15.654331

A novel strategy to mitigate Corynebacterium bovis-associated hyperkeratosis (CAH) in athymic nude mice

Michelson, A.·Cheleuitte-Nieves, C.·Nickerson, K.·Dobtsis, I.·Miranda, I.·Ricart Arbona, R. J.·Wipf, J.·Lipman, N. S.
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Abstract

Nude mice were inoculated with a non-pathogenic Cb isolate (NPI) or Corynebacterium amycolatum (Ca) to assess whether either could prevent skin lesions following inoculation with a pathogenic Cb isolate (PI). Crl:NU(NCr)-Foxn1nu mice (n=6/group) were randomized into 6 groups: NPI (108 CFU); Ca (108 CFU); NPI or Ca followed 2 weeks later by PI (104 CFU); and negative and positive controls receiving sterile media or the PI (104 CFU), respectively. Colonization was assessed biweekly using isolate-specific PCR assays. Skin lesions were scored 0 - 5 daily for 4 or 6 weeks at which point skin biopsies were collected, evaluated and scored. No mice inoculated with the NPI and subsequently infected with the PI developed clinical signs nor was a significant amount of the PI detected by PCR. Mice inoculated with Ca before the PI developed milder, delayed skin lesions reaching a significantly lower mean peak clinical score (MPCS; 1.2 +/- 0.4) as compared to the positive control (MPCS 2.5 +/- 0.5). The Ca inoculated mice with and without PI had similar total histopathology scores, both of which were significantly higher than the mice inoculated with the NPI followed by the PI. These results led to evaluation of a practical exposure strategy in which nude mice (n=6/group) were housed on NPI-seeded bedding (SB) for 3 or 7 days prior to PI administration; mice housed on Cb-free bedding served as controls. Only 1 of 12 mice housed on SB receiving the PI developed CAH (peak score of 4), whereas all unvaccinated mice receiving the PI developed CAH (MPCS 2.83 +/- 0.69). The PI was not detected in the SB + PI groups until 21 days post-infection with the PI. There was no significant difference in total histopathology scores across groups, but the histopathology scores were lower in mice receiving the SB.

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Michelson, A., Cheleuitte-Nieves, C., Nickerson, K., Dobtsis, I., Miranda, I., Ricart Arbona, R. J., Wipf, J., Lipman, N. S.. 2025-05-15. A novel strategy to mitigate Corynebacterium bovis-associated hyperkeratosis (CAH) in athymic nude mice. https://doi.org/10.1101/2025.05.15.654331

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