TY - JOUR
T1 - Low-dose inoculation of Escherichia coli achieves robust vaginal colonization and results in ascending infection accompanied by severe uterine inflammation in mice
AU - O’Brien, Valerie P.
AU - Gilbert, Nicole M.
AU - Lebratti, Tania
AU - Agarwal, Kavita
AU - Foster, Lynne
AU - Shin, Haina
AU - Lewis, Amanda L.
N1 - Funding Information:
This work was supported by the National Institutes of Health NIAID [R01 AI114635 to ALL, https://www.niaid.nih.gov/] and NIDDK [R21 DK092586 to ALL, https://www.niddk.nih.gov/]; We thank Scott Hultgren for bacterial strains and Jennifer Lodge for the use of her microscope. This work was supported by the National Institutes of Health NIAID [R01 AI114635 to ALL] and NIDDK [R21 DK092586 to ALL]; and by the National Science Foundation [Graduate Research Fellowship to VPO #DGE? 1143954]. Some of the animal studies were performed in a facility supported by the NCRR [C06 RR015502]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Publisher Copyright:
© 2019 O’Brien et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2019/7/1
Y1 - 2019/7/1
N2 - Escherichia coli infection of the female reproductive tract is a significant cause of disease in humans and animals, but simple animal models are lacking. Here we report that vaginal inoculation of uropathogenic E. coli strains UTI89 and CFT073 in non-pregnant, estrogen-treated mice resulted in robust colonization of the vagina and uterine horns, whereas titers of the lab strain MG1655 were significantly lower. Non-estrogenized mice also became colonized, but there was more variation in titers. A dose of 104 colony-forming units (CFU) UTI89 was sufficient to result in colonization in all estrogenized mice, and we also observed bacterial transfer between inoculated and uninoculated estrogenized cage mates. UTI89 infection led to inflammation and leukocyte infiltration into the uterine horns as evidenced by tissue histology. Flow cytometry experiments revealed that neutrophil, monocyte and eosinophil populations were significantly increased in infected uterine horns. This model is a simple way to study host-pathogen interactions in E. coli vaginal colonization and uterine infection. There are immediate implications for investigators studying urinary tract infection using mouse models, as few E. coli are required to achieve reproductive colonization, resulting in an additional, underappreciated mucosal reservoir.
AB - Escherichia coli infection of the female reproductive tract is a significant cause of disease in humans and animals, but simple animal models are lacking. Here we report that vaginal inoculation of uropathogenic E. coli strains UTI89 and CFT073 in non-pregnant, estrogen-treated mice resulted in robust colonization of the vagina and uterine horns, whereas titers of the lab strain MG1655 were significantly lower. Non-estrogenized mice also became colonized, but there was more variation in titers. A dose of 104 colony-forming units (CFU) UTI89 was sufficient to result in colonization in all estrogenized mice, and we also observed bacterial transfer between inoculated and uninoculated estrogenized cage mates. UTI89 infection led to inflammation and leukocyte infiltration into the uterine horns as evidenced by tissue histology. Flow cytometry experiments revealed that neutrophil, monocyte and eosinophil populations were significantly increased in infected uterine horns. This model is a simple way to study host-pathogen interactions in E. coli vaginal colonization and uterine infection. There are immediate implications for investigators studying urinary tract infection using mouse models, as few E. coli are required to achieve reproductive colonization, resulting in an additional, underappreciated mucosal reservoir.
UR - http://www.scopus.com/inward/record.url?scp=85069862090&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0219941
DO - 10.1371/journal.pone.0219941
M3 - Article
C2 - 31329630
AN - SCOPUS:85069862090
VL - 14
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 7
M1 - e0219941
ER -