Biology subjects

Nickerson, K.

Publications and source records attributed to Nickerson, K..

3 recordsLinked to original sources

bioRxiv2026

Skin and Gut Microbiome Features Associated with Resistance to Corynebacterium bovis-Associated Disease in Nude Mice (Mus musculus)

Corynebacterium bovis is an important opportunistic pathogen of immunodeficient mice and the etiologic agent of Corynebacterium-associated hyperkeratosis (CAH). Although disease severity varies, specific vendor-derived microbiomes have been shown to protect against CAH. Preinoculation with nonpathogenic Corynebacterium amycolatum prior to C. bovis infection has been demonstrated to limit disease severity. To define community features associated with protection, axenic outbred athymic nude mice stocks (A, B, and C) were reassociated with donor microbiomes from four vendor sources (A1, A2, B, and C) and topically challenged with C. bovis. C. amycolatum was added to the A1 microbiome in a separate group. Skin (Stock A) and fecal (Stocks A, B, and C) microbiomes were evaluated at 21 days post-inoculation via shotgun metagenomic sequencing. The A2 microbiome, previously associated with resistance to clinical disease and minimal skin pathology, exhibited greater cutaneous microbial evenness after challenge and significantly lower relative abundance of C. bovis than all other microbiome groups. Addition of C. amycolatum to the A1 microbiome did not fully confer disease protection and relative abundance was low, suggesting that sustained colonization by this organism was insufficient to explain the protective phenotype seen with the A2 microbiome. C. kroppenstedtii was detected in all A2 skin samples and was absent from all other groups. Several anaerobic taxa, including Duncaniella dubosii, D. muris, Bacteroides caecimuris, and Muribaculum gordoncarteri, were uniquely detected or enriched in the A2-associated microbiome, whereas Mammaliicoccus lentus and Staphylococcus nepalensis were absent from A2 but present in all nonprotective groups. Gut alpha diversity did not differ significantly among microbiomes, although several taxa, including segmented filamentous bacteria, were enriched in A2 feces. These findings associate resistance to CAH with preservation of cutaneous community structure, suppression of C. bovis prominence, and distinct microbial taxa. The identified organisms represent candidates for future mechanistic studies of microbiome-mediated colonization resistance.

zoology↗

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↗

bioRxiv2019

Murine lupus is Neutrophil Elastase-independent in the MRL.Faslprmodel

Loss of tolerance to nuclear antigens and multisystem tissue destruction is a hallmark of systemic lupus erythematosus (SLE). Although the source of autoantigen in lupus remains elusive, a compelling hypothetical source is dead cell debris that drives autoimmune activation. Prior reports suggest that neutrophil extracellular traps (NETs) and their associated death pathway, NETosis, are sources of autoantigen in SLE. However, others and we have shown that inhibition of NETs by targeting the NADPH oxidase complex and peptidylarginine deiminase 4 (PADI4) did not ameliorate disease in spontaneous murine models of SLE. Furthermore, myeloperoxidase and PADI4 deletion did not inhibit induced lupus. Since NET formation may occur independently of any one mediator, to address this controversy, we genetically deleted an additional important mediator of NETs and neutrophil effector function, neutrophil elastase (ELANE), in the MRL.Faslpr model of SLE. ELANE deficiency, and by extension ELANE-dependent NETs, had no effect on SLE nephritis, dermatitis, anti-self response, or immune composition in MRL.Faslpr mice. Taken together with prior data from our group and others, these data further challenge the paradigm that NETs and neutrophils are pathogenic in SLE.

immunology↗