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Microbial Colonization Coordinates the Pathogenesis of a Klebsiella pneumoniae Infant Isolate
Jillian L Pope1, Ye Yang1, Rachel C Newsome1
1Department of Medicine, University of Florida, Gainesville, Florida, USA.
Insights
Klebsiella pneumoniae from infant stool can cause inflammation and DNA damage. Its pathogenicity is influenced by gut microbiota composition, highlighting the importance of early colonization patterns.
Area of Science:
- Microbiology
- Gastroenterology
- Immunology
Background:
- Enterobacteriaceae, including Klebsiella pneumoniae, are early gut colonizers in neonates.
- Some pathobionts, like K. pneumoniae, can cause disease under specific conditions.
- The interaction between developing gut microbiota and pathobiont virulence is not well understood.
Purpose of the Study:
- To investigate the functional interaction between K. pneumoniae colonization patterns and host response.
- To determine the pathogenic potential of an infant-derived K. pneumoniae isolate (51-5) carrying the pks genotoxin island.
- To assess the impact of microbiota on K. pneumoniae-induced inflammation and tumor development.
Main Methods:
- In vitro studies using intestinal epithelial cells, macrophages, and splenocytes.
- Gnotobiotic experiments in Il10 knockout mice to assess in vivo inflammation.
- Tumorigenesis studies in ApcMin/+; Il10 knockout mice.
- Analysis of proinflammatory gene expression, DNA damage, and cell cycle arrest.
Main Results:
- K. pneumoniae 51-5 upregulated proinflammatory genes in vitro and induced intestinal inflammation in vivo.
- The isolate accelerated inflammation onset in Il10 knockout mice, especially with naturally acquired microbiota.
- K. pneumoniae 51-5 induced DNA damage and cell cycle arrest.
- Tumor development in ApcMin/+; Il10 knockout mice was not significantly affected by the absence of the colibactin-activating enzyme ClbP.
Conclusions:
- Pathogenicity of the infant K. pneumoniae isolate is sensitive to microbial colonization status.
- Early colonization by pathobionts like K. pneumoniae can have significant health implications.
- Further research is needed to understand the complex interplay between microbiota and pathobiont virulence in neonates.
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.
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