Biology subjects

Ritter, A. C.

Publications and source records attributed to Ritter, A. C..

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↗

bioRxiv2026

Microbiome-Dependent Protection Against Corynebacterium bovis-Associated Hyperkeratosis in Nude Mice (Mus musculus)

Corynebacterium bovis, the cause of Corynebacterium-associated hyperkeratosis (CAH), is an important pathogen in immunocompromised mice that is difficult to eliminate and can confound research outcomes. We recently observed that CAH severity varies among outbred athymic nude mouse stocks, but the relative contributions of host genetics and the microbiome remain unclear. We hypothesized that disease course and severity vary based on host genetic stock and/or microbiome composition. Three nude mouse stocks were rederived into the axenic state and either monoinfected with a pathogenic C. bovis isolate (104; CFU) or given sterile media (n=6/group). Axenic mice were also reassociated with their source microbiome or microbiomes from three other stocks with known differences in CAH severity, then inoculated with C. bovis (n=6) or sterile media (n=2). In a separate experiment, one axenic stock was used to assess the role of C. amycolatum via monoinfection, monoinfection followed by C. bovis challenge, or addition to a nonprotective microbiome followed by C. bovis challenge. Mice were monitored daily for 21 days and scored for skin lesions (0-5). C. bovis monoinfected mice developed disease comparable in severity and timing to conventionally raised controls. Notably, reassociation with Vendor A2s microbiome prevented clinical lesions and reduced histopathologic changes across all stocks. While C. amycolatum as a monoinfection did not cause disease nor reduce disease severity following C. bovis challenge, it delayed the onset and lowered peak scores when added to a non-protective microbiome. These findings demonstrate that C. bovis can cause CAH as a monoinfection, that both host genetics and microbiome composition influence disease progression, and, together with prior work, support its role as the etiologic agent consistent with Kochs postulates. Identifying protective microbiome constituents may inform strategies to reduce disease burden in susceptible mice.

microbiology↗

bioRxiv2022

Assessing Mouse Kidney Parvovirus' Ability to Confound Research by Examining its Effects on Renally Excreted Chemotherapeutics and its Impact on Pathologic Endpoints in the Adenine Model of Chronic Kidney Disease

Mouse kidney parvovirus (MKPV) causes inclusion body nephropathy in severely immunocompromised mice and renal interstitial inflammation in immunocompetent mice. The purpose of this 2-part study was to determine the impact that MKPV may have on preclinical models as it relates to the pharmacokinetics of chemotherapeutics as well as its impact on the adenine diet model of chronic kidney disease. To assess the impact of MKPV on pharmacokinetics of 2 renally excreted chemotherapeutics commonly used in preclinical oncology studies, methotrexate and lenalidomide, blood and urine drug concentrations were measured in MKPV-infected or uninfected immunodeficient NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) and immunocompetent C57BL/6NCrl (B6) female mice. Differences in plasma pharmacokinetics were observed for methotrexate, but not for lenalidomide. Differences were most profound between uninfected NSG and B6 mice. The area under the curve (AUC) of methotrexate was 1.5-fold higher in uninfected NSG mice compared to infected NSG mice, 1.9-fold higher in infected B6 mice compared to uninfected B6 mice, and 4.3-fold higher in uninfected NSG mice compared to uninfected B6 mice. Renal clearance of both drugs was not impacted by MKPV infection but was generally lower in NSG mice. To assess the impact of MKPV on the adenine diet model of chronic kidney disease, MKPV-infected and uninfected B6 female mice were fed a 0.2% adenine diet and clinical and histopathologic features of disease were assessed over 8 weeks. Infection with MKPV did not have a significant impact on serum biomarkers of renal function such as BUN, creatinine, and SDMA; urine chemistry; or hemogram. However, infection did impact select histologic outcomes. MKPV-infected mice had significantly more foci of interstitial lymphoplasmacytic infiltrates than uninfected mice after 4 and 8 weeks of diet consumption, and significantly less interstitial fibrosis at week 8. Macrophage infiltrates and renal tubular injury, assessed using various immunohistochemical stains, were similar between groups. Together, these findings indicate that MKPV infection had minimal impact on the renal excretion of 2 chemotherapeutics and serum biomarkers of renal function. However, infection significantly impacted select histologic features of renal disease in the adenine diet model. While MKPV-free mice should be used in biomedical research, it is of the utmost importance in studies evaluating renal histology as an experimental outcome.

pathology↗