Biology subjects

Michelson, A.

Publications and source records attributed to Michelson, A..

2 recordsLinked to original sources

bioRxiv2025

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

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.

microbiology↗

bioRxiv2024

The Impact of Host Genetics and/or its Microbiota on the Severity of Corynebacterium-Associated Hyperkeratosis in Outbred Athymic Nude Mice

Corynebacterium bovis (Cb), the etiology of Corynebacterium-associated hyperkeratosis (CAH) in nude mice, may impact research outcomes. Little is known about the differences in the course and severity of CAH in different outbred athymic nude mice stocks. Three genetic stocks (designated A, B, and C), 1 of which was obtained from 2 geographically separate colonies with distinct microbiota (A1 and A2), were inoculated topically with 1 x 108 CFUs of a pathogenic Cb field isolate (#7894; n = 6/stock) or sterile media (n=2/stock; controls). Clinical signs were assessed daily and scored 0 - 5 based on lesion severity. Mice were euthanized at 14 (A1, A2, B, and C) or 28 (B) days-post-inoculation (dpi), macroscopic changes documented, and 6 skin samples per mouse were obtained and histologically scored 0 - 4 based on the presence and severity of hyperkeratosis, acanthosis, inflammation, and bacterial colonies. No stock A1 or control mice developed clinical disease; 1 of 6 stock B mice developed mild CAH (mean peak clinical score [MPCS] - 0.33) at 14 dpi (14 day group) and 2 of 6 stock B (28 day group) developed mild CAH at 15 dpi (MPCS -0.33); and, all stock C and A2 mice developed significant clinical signs at 5 dpi (MPCS - 2.5 and 3, respectively) which resolved by 11 dpi. Despite differences in clinical presentation, all Cb-infected mice had hyperkeratosis and/or acanthosis with associated bacterial colonies. Stocks A1 and B, which had minimal or no clinical signs, were colonized with Corynebacterium amycolatum (Ca). In contrast, stocks C and A2 were not colonized with Ca, raising the possibility that Ca and/or other components of the skin microbiota may mitigate clinical signs but not necessarily all histopathologic changes associated with infection. These findings suggest host genetics and/or the skin microbiota can markedly influence the presentation of CAH in nude mice.

microbiology↗