Microbial Colonization Coordinates the Pathogenesis of a Klebsiella pneumoniae Infant Isolate View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Jillian L. Pope, Ye Yang, Rachel C. Newsome, Wei Sun, Xiaolun Sun, Maria Ukhanova, Josef Neu, Jean-Pierre Issa, Volker Mai, Christian Jobin

ABSTRACT

Enterobacteriaceae are among the first colonizers of neonate intestine. Members of this family, such as Escherichia and Klebsiella, are considered pathobionts and as such are capable of inducing local and systemic disease under specific colonization circumstances. Interplay between developing microbiota and pathogenic function of pathobionts are poorly understood. In this study, we investigate the functional interaction between various colonization patterns on an early colonizer, K. pneumoniae. K. pneumoniae 51-5 was isolated from stool of a healthy, premature infant, and found to contain the genotoxin island pks associated with development of colorectal cancer. Using intestinal epithelial cells, macrophages, and primary splenocytes, we demonstrate K. pneumoniae 51-5 upregulates expression of proinflammatory genes in vitro. Gnotobiotic experiments in Il10-/- mice demonstrate the neonate isolate induces intestinal inflammation in vivo, with increased expression of proinflammatory genes. Regulation of microbiota assembly revealed K. pneumoniae 51-5 accelerates onset of inflammation in Il10-/- mice, most significantly when microbiota is naturally acquired. Furthermore, K. pneumoniae 51-5 induces DNA damage and cell cycle arrest. Interestingly, K. pneumoniae 51-5 induced tumors in ApcMin/+; Il10-/- mice was not significantly affected by absence of colibactin activating enzyme, ClbP. These findings demonstrate pathogenicity of infant K. pneumoniae isolate is sensitive to microbial colonization status. More... »

PAGES

3380

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-019-39887-8

DOI

http://dx.doi.org/10.1038/s41598-019-39887-8

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1112510786

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30833613


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