Biology subjects

Cheleuitte-Nieves, C.

Publications and source records attributed to Cheleuitte-Nieves, C..

3 recordsLinked to original sources

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↗

bioRxiv2022

Establishing the Median Infectious Dose (ID50) and Characterizing the Clinical Manifestations of Mouse, Rat, Cow, and Human Corynebacterium bovis Isolates in Select Immunocompromised Mouse Strains

Corynebacterium bovis (Cb), the etiology of hyperkeratotic dermatitis in various immunocompromised mouse strains, significantly impacts research in which infected mice are used. Although Cb has been isolated from a variety of species, including mice, rats, cows, and humans, little is known about the differences in the infectivity and clinical disease in mice associated with unique isolates. The infectious dose yielding colonization of 50% of the exposed population (ID50) and any associated clinical disease was determined for mouse (n=3), rat (n=1), cow (n=1), and human (n=2) Cb isolates in athymic nude mice (Hsd:Athymic Nude-Foxn1nu). The same investigations were undertaken comparing 2 of these murine isolates in 2 furred immunocompromised mouse strains (NSG [NOD.Cg-PrkdcscidIl2rgtm1Wjl/Sz] and NSG-S [NOD.Cg-PrkdcscidIl2rgtm1WjlTg(CMV-IL3,CSF2,KITLG)1Eav/MloySzJ]). To determine the ID50, mice (n=6/dose; 3 of each sex) were inoculated topically with 1 to 108 bacteria (10-fold increments) of each Cb isolate. Mice were scored (0 to 5) daily based on the severity of clinical signs for 14 days. On day 7 and 14 post-inoculation (PI), buccal and dorsal skin swabs were evaluated by aerobic culture to determine infection status. The mouse isolates yielded a lower ID50 (58 to 1,000 bacteria) as compared to the bovine (6,460 to 7,498 bacteria) and rat (10,000 bacteria) Cb isolates. Mice were not colonized and disease did not result when inoculated with human isolates. Mouse isolates produced varying clinical disease severity in nude mice (max score/isolate: 0 to 5). Despite significant immunodeficiency, furred NSG and NSG-S mice required a considerably higher (1,000- to 3,000-fold) inoculum to become colonized as compared to athymic nude mice. Once colonized, clinically detectable hyperkeratosis did not develop in these strains until 18 to 22 days PI. In contrast, in athymic nude mice that developed clinically detectable disease, hyperkeratosis was observed 6 to 14 days PI. In conclusion, there are significant differences in Cbs ID50, disease course, and severity between Cb isolates and among immunodeficient mouse strains.

microbiology↗

bioRxiv2022

Reemergence of the Murine Bacterial Pathogen Chlamydia muridarum in Laboratory Mouse Colonies

Chlamydia muridarum (Cm) was detected in mice from 2 colonies with lymphoplasmacytic pulmonary infiltrates using PCR and immunohistochemistry. This discovery was unexpected as Cm infection had not been reported in laboratory mice since the 1940s. A Cm specific PCR assay was developed and testing implemented for resident colonies from 8 vivaria from 3 academic institutions, 58 incoming mouse shipments from 39 academic institutions, and mice received from 55 commercial breeding colonies (4 vendors). To estimate Cms global prevalence in laboratory colonies, a database containing 11,387 metagenomic fecal microbiota samples from 120 institutions and a cohort of 900 diagnostic samples from 96 institutions were examined. Results indicate significant prevalence amongst academic institutions with Cm detected in 62.9% of soiled bedding sentinels from 3 institutions; 32.7% of incoming mouse shipments from 39 academic institutions; 14.2% of 120 institutions submitting microbiota samples; and 16.2% of the diagnostic sample cohort. All samples from commercial breeding colonies were negative. Additionally, naive NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice exposed to Cm shedding mice and their soiled bedding developed clinical disease 21 to 28 days following exposure. These mice had a moderate-to-severe histiocytic and neutrophilic bronchointerstitial pneumonia with respiratory epithelium demonstrating inclusions, chlamydial major outer membrane protein immunostaining, and hybridization with a Cm reference sequence (GenBank accession no. U68436). Cm was isolated on HeLa 229 cells from lungs, cecum, and feces of a Cm infected NSG mouse. The considerable prevalence of Cm is likely attributed to widespread global interinstitutional distribution of unique mouse strains and failure to recognize that some of these mice were from enzootically infected colonies. Given that experimental Cm colonization of mice results in a robust immune response and, on occasion, pathology, natural infection may confound experimental results. Therefore, Cm should be excluded and eradicated from endemically infected laboratory mouse colonies.

microbiology↗