Modelling the Gastrointestinal Carriage of Klebsiella pneumoniae Infections

Klebsiella pneumoniae is one of the pathogens that is sweeping the world in the antibiotic resistance pandemic. Klebsiella colonizes the nasopharynx and the gut of healthy subjects in an asymptomatic manner, making gut colonization a requisite for infection. This makes it essential to understand the...

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Published inmBio Vol. 14; no. 1; p. e0312122
Main Authors Calderon-Gonzalez, Ricardo, Lee, Alix, Lopez-Campos, Guillermo, Hancock, Steven J., Sa-Pessoa, Joana, Dumigan, Amy, McMullan, Ronan, Campbell, Eric L., Bengoechea, Jose A.
Format Journal Article
LanguageEnglish
Published United States American Society for Microbiology 28.02.2023
Subjects
Animals
Anti-Bacterial Agents - pharmacology
capsule polysaccharide
Gastrointestinal Tract - pathology
gut colonization
Host-Microbial Interactions
Humans
Inflammation
Klebsiella Infections - epidemiology
Klebsiella pneumoniae
Mice
Research Article
type VI secretion system
type VI secretion system
capsule polysaccharide
Klebsiella pneumoniae
gut colonization
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Abstract Klebsiella pneumoniae is one of the pathogens that is sweeping the world in the antibiotic resistance pandemic. Klebsiella colonizes the nasopharynx and the gut of healthy subjects in an asymptomatic manner, making gut colonization a requisite for infection. This makes it essential to understand the gastrointestinal carriage in preventing Klebsiella infections. Klebsiella pneumoniae is a leading cause of nosocomial and community acquired infections, making K. pneumoniae the pathogen that is associated with the second largest number of deaths attributed to any antibiotic resistant infection. K. pneumoniae colonizes the nasopharynx and the gastrointestinal tract in an asymptomatic manner without dissemination to other tissues. Importantly, gastrointestinal colonization is a requisite for infection. Our understanding of K. pneumoniae colonization is still based on interrogating mouse models in which animals are pretreated with antibiotics to disturb the colonization resistance imposed by the gut microbiome. In these models, infections disseminate to other tissues. Here, we report a murine model to allow for the study of the gastrointestinal colonization of K. pneumoniae without tissue dissemination. Hypervirulent and antibiotic resistant strains stably colonize the gastrointestinal tract of in an inbred mouse population without antibiotic treatment. The small intestine is the primary site of colonization and is followed by a transition to the colon over time, without dissemination to other tissues. Our model recapitulates the disease dynamics of the metastatic K. pneumoniae strains that are able to disseminate from the gastrointestinal tract to other sterile sites. Colonization is associated with mild to moderate histopathology, no significant inflammation, and no effect on the richness of the microbiome. Our model sums up the clinical scenario in which antibiotic treatment disturbs the colonization of K. pneumoniae and results in dissemination to other tissues. Finally, we establish that the capsule polysaccharide is necessary for the colonization of the large intestine, whereas the type VI secretion system contributes to colonization across the gastrointestinal tract. IMPORTANCE Klebsiella pneumoniae is one of the pathogens that is sweeping the world in the antibiotic resistance pandemic. Klebsiella colonizes the nasopharynx and the gut of healthy subjects in an asymptomatic manner, making gut colonization a requisite for infection. This makes it essential to understand the gastrointestinal carriage in preventing Klebsiella infections. Current research models rely on the perturbation of the gut microbiome by antibiotics, resulting in an invasive infection. Here, we report a new model of K. pneumoniae gut colonization that recapitulates key features of the asymptomatic human gastrointestinal tract colonization. In our model, there is no need to disturb the microbiota to achieve stable colonization, and there is no dissemination to other tissues. Our model sums up the clinical scenario in which antibiotic treatment triggers invasive infection. We envision that our model will be an excellent platform upon which to investigate factors enhancing colonization and invasive infections and to test therapeutics to eliminate Klebsiella asymptomatic colonization.
AbstractList ABSTRACT Klebsiella pneumoniae is a leading cause of nosocomial and community acquired infections, making K. pneumoniae the pathogen that is associated with the second largest number of deaths attributed to any antibiotic resistant infection. K. pneumoniae colonizes the nasopharynx and the gastrointestinal tract in an asymptomatic manner without dissemination to other tissues. Importantly, gastrointestinal colonization is a requisite for infection. Our understanding of K. pneumoniae colonization is still based on interrogating mouse models in which animals are pretreated with antibiotics to disturb the colonization resistance imposed by the gut microbiome. In these models, infections disseminate to other tissues. Here, we report a murine model to allow for the study of the gastrointestinal colonization of K. pneumoniae without tissue dissemination. Hypervirulent and antibiotic resistant strains stably colonize the gastrointestinal tract of in an inbred mouse population without antibiotic treatment. The small intestine is the primary site of colonization and is followed by a transition to the colon over time, without dissemination to other tissues. Our model recapitulates the disease dynamics of the metastatic K. pneumoniae strains that are able to disseminate from the gastrointestinal tract to other sterile sites. Colonization is associated with mild to moderate histopathology, no significant inflammation, and no effect on the richness of the microbiome. Our model sums up the clinical scenario in which antibiotic treatment disturbs the colonization of K. pneumoniae and results in dissemination to other tissues. Finally, we establish that the capsule polysaccharide is necessary for the colonization of the large intestine, whereas the type VI secretion system contributes to colonization across the gastrointestinal tract. IMPORTANCE Klebsiella pneumoniae is one of the pathogens that is sweeping the world in the antibiotic resistance pandemic. Klebsiella colonizes the nasopharynx and the gut of healthy subjects in an asymptomatic manner, making gut colonization a requisite for infection. This makes it essential to understand the gastrointestinal carriage in preventing Klebsiella infections. Current research models rely on the perturbation of the gut microbiome by antibiotics, resulting in an invasive infection. Here, we report a new model of K. pneumoniae gut colonization that recapitulates key features of the asymptomatic human gastrointestinal tract colonization. In our model, there is no need to disturb the microbiota to achieve stable colonization, and there is no dissemination to other tissues. Our model sums up the clinical scenario in which antibiotic treatment triggers invasive infection. We envision that our model will be an excellent platform upon which to investigate factors enhancing colonization and invasive infections and to test therapeutics to eliminate Klebsiella asymptomatic colonization.
Klebsiella pneumoniae is a leading cause of nosocomial and community acquired infections, making K. pneumoniae the pathogen that is associated with the second largest number of deaths attributed to any antibiotic resistant infection. K. pneumoniae colonizes the nasopharynx and the gastrointestinal tract in an asymptomatic manner without dissemination to other tissues. Importantly, gastrointestinal colonization is a requisite for infection. Our understanding of K. pneumoniae colonization is still based on interrogating mouse models in which animals are pretreated with antibiotics to disturb the colonization resistance imposed by the gut microbiome. In these models, infections disseminate to other tissues. Here, we report a murine model to allow for the study of the gastrointestinal colonization of K. pneumoniae without tissue dissemination. Hypervirulent and antibiotic resistant strains stably colonize the gastrointestinal tract of in an inbred mouse population without antibiotic treatment. The small intestine is the primary site of colonization and is followed by a transition to the colon over time, without dissemination to other tissues. Our model recapitulates the disease dynamics of the metastatic K. pneumoniae strains that are able to disseminate from the gastrointestinal tract to other sterile sites. Colonization is associated with mild to moderate histopathology, no significant inflammation, and no effect on the richness of the microbiome. Our model sums up the clinical scenario in which antibiotic treatment disturbs the colonization of K. pneumoniae and results in dissemination to other tissues. Finally, we establish that the capsule polysaccharide is necessary for the colonization of the large intestine, whereas the type VI secretion system contributes to colonization across the gastrointestinal tract. Klebsiella pneumoniae is one of the pathogens that is sweeping the world in the antibiotic resistance pandemic. colonizes the nasopharynx and the gut of healthy subjects in an asymptomatic manner, making gut colonization a requisite for infection. This makes it essential to understand the gastrointestinal carriage in preventing Klebsiella infections. Current research models rely on the perturbation of the gut microbiome by antibiotics, resulting in an invasive infection. Here, we report a new model of K. pneumoniae gut colonization that recapitulates key features of the asymptomatic human gastrointestinal tract colonization. In our model, there is no need to disturb the microbiota to achieve stable colonization, and there is no dissemination to other tissues. Our model sums up the clinical scenario in which antibiotic treatment triggers invasive infection. We envision that our model will be an excellent platform upon which to investigate factors enhancing colonization and invasive infections and to test therapeutics to eliminate Klebsiella asymptomatic colonization.
Klebsiella pneumoniae is a leading cause of nosocomial and community acquired infections, making K. pneumoniae the pathogen that is associated with the second largest number of deaths attributed to any antibiotic resistant infection. K. pneumoniae colonizes the nasopharynx and the gastrointestinal tract in an asymptomatic manner without dissemination to other tissues. Importantly, gastrointestinal colonization is a requisite for infection. Our understanding of K. pneumoniae colonization is still based on interrogating mouse models in which animals are pretreated with antibiotics to disturb the colonization resistance imposed by the gut microbiome. In these models, infections disseminate to other tissues. Here, we report a murine model to allow for the study of the gastrointestinal colonization of K. pneumoniae without tissue dissemination. Hypervirulent and antibiotic resistant strains stably colonize the gastrointestinal tract of in an inbred mouse population without antibiotic treatment. The small intestine is the primary site of colonization and is followed by a transition to the colon over time, without dissemination to other tissues. Our model recapitulates the disease dynamics of the metastatic K. pneumoniae strains that are able to disseminate from the gastrointestinal tract to other sterile sites. Colonization is associated with mild to moderate histopathology, no significant inflammation, and no effect on the richness of the microbiome. Our model sums up the clinical scenario in which antibiotic treatment disturbs the colonization of K. pneumoniae and results in dissemination to other tissues. Finally, we establish that the capsule polysaccharide is necessary for the colonization of the large intestine, whereas the type VI secretion system contributes to colonization across the gastrointestinal tract.
Klebsiella pneumoniae is a leading cause of nosocomial and community acquired infections, making K. pneumoniae the pathogen that is associated with the second largest number of deaths attributed to any antibiotic resistant infection. K. pneumoniae colonizes the nasopharynx and the gastrointestinal tract in an asymptomatic manner without dissemination to other tissues. Importantly, gastrointestinal colonization is a requisite for infection. Our understanding of K. pneumoniae colonization is still based on interrogating mouse models in which animals are pretreated with antibiotics to disturb the colonization resistance imposed by the gut microbiome. In these models, infections disseminate to other tissues. Here, we report a murine model to allow for the study of the gastrointestinal colonization of K. pneumoniae without tissue dissemination. Hypervirulent and antibiotic resistant strains stably colonize the gastrointestinal tract of in an inbred mouse population without antibiotic treatment. The small intestine is the primary site of colonization and is followed by a transition to the colon over time, without dissemination to other tissues. Our model recapitulates the disease dynamics of the metastatic K. pneumoniae strains that are able to disseminate from the gastrointestinal tract to other sterile sites. Colonization is associated with mild to moderate histopathology, no significant inflammation, and no effect on the richness of the microbiome. Our model sums up the clinical scenario in which antibiotic treatment disturbs the colonization of K. pneumoniae and results in dissemination to other tissues. Finally, we establish that the capsule polysaccharide is necessary for the colonization of the large intestine, whereas the type VI secretion system contributes to colonization across the gastrointestinal tract. IMPORTANCE Klebsiella pneumoniae is one of the pathogens that is sweeping the world in the antibiotic resistance pandemic. Klebsiella colonizes the nasopharynx and the gut of healthy subjects in an asymptomatic manner, making gut colonization a requisite for infection. This makes it essential to understand the gastrointestinal carriage in preventing Klebsiella infections. Current research models rely on the perturbation of the gut microbiome by antibiotics, resulting in an invasive infection. Here, we report a new model of K. pneumoniae gut colonization that recapitulates key features of the asymptomatic human gastrointestinal tract colonization. In our model, there is no need to disturb the microbiota to achieve stable colonization, and there is no dissemination to other tissues. Our model sums up the clinical scenario in which antibiotic treatment triggers invasive infection. We envision that our model will be an excellent platform upon which to investigate factors enhancing colonization and invasive infections and to test therapeutics to eliminate Klebsiella asymptomatic colonization.Klebsiella pneumoniae is a leading cause of nosocomial and community acquired infections, making K. pneumoniae the pathogen that is associated with the second largest number of deaths attributed to any antibiotic resistant infection. K. pneumoniae colonizes the nasopharynx and the gastrointestinal tract in an asymptomatic manner without dissemination to other tissues. Importantly, gastrointestinal colonization is a requisite for infection. Our understanding of K. pneumoniae colonization is still based on interrogating mouse models in which animals are pretreated with antibiotics to disturb the colonization resistance imposed by the gut microbiome. In these models, infections disseminate to other tissues. Here, we report a murine model to allow for the study of the gastrointestinal colonization of K. pneumoniae without tissue dissemination. Hypervirulent and antibiotic resistant strains stably colonize the gastrointestinal tract of in an inbred mouse population without antibiotic treatment. The small intestine is the primary site of colonization and is followed by a transition to the colon over time, without dissemination to other tissues. Our model recapitulates the disease dynamics of the metastatic K. pneumoniae strains that are able to disseminate from the gastrointestinal tract to other sterile sites. Colonization is associated with mild to moderate histopathology, no significant inflammation, and no effect on the richness of the microbiome. Our model sums up the clinical scenario in which antibiotic treatment disturbs the colonization of K. pneumoniae and results in dissemination to other tissues. Finally, we establish that the capsule polysaccharide is necessary for the colonization of the large intestine, whereas the type VI secretion system contributes to colonization across the gastrointestinal tract. IMPORTANCE Klebsiella pneumoniae is one of the pathogens that is sweeping the world in the antibiotic resistance pandemic. Klebsiella colonizes the nasopharynx and the gut of healthy subjects in an asymptomatic manner, making gut colonization a requisite for infection. This makes it essential to understand the gastrointestinal carriage in preventing Klebsiella infections. Current research models rely on the perturbation of the gut microbiome by antibiotics, resulting in an invasive infection. Here, we report a new model of K. pneumoniae gut colonization that recapitulates key features of the asymptomatic human gastrointestinal tract colonization. In our model, there is no need to disturb the microbiota to achieve stable colonization, and there is no dissemination to other tissues. Our model sums up the clinical scenario in which antibiotic treatment triggers invasive infection. We envision that our model will be an excellent platform upon which to investigate factors enhancing colonization and invasive infections and to test therapeutics to eliminate Klebsiella asymptomatic colonization.
Klebsiella pneumoniae is one of the pathogens that is sweeping the world in the antibiotic resistance pandemic. Klebsiella colonizes the nasopharynx and the gut of healthy subjects in an asymptomatic manner, making gut colonization a requisite for infection. This makes it essential to understand the gastrointestinal carriage in preventing Klebsiella infections. Klebsiella pneumoniae is a leading cause of nosocomial and community acquired infections, making K. pneumoniae the pathogen that is associated with the second largest number of deaths attributed to any antibiotic resistant infection. K. pneumoniae colonizes the nasopharynx and the gastrointestinal tract in an asymptomatic manner without dissemination to other tissues. Importantly, gastrointestinal colonization is a requisite for infection. Our understanding of K. pneumoniae colonization is still based on interrogating mouse models in which animals are pretreated with antibiotics to disturb the colonization resistance imposed by the gut microbiome. In these models, infections disseminate to other tissues. Here, we report a murine model to allow for the study of the gastrointestinal colonization of K. pneumoniae without tissue dissemination. Hypervirulent and antibiotic resistant strains stably colonize the gastrointestinal tract of in an inbred mouse population without antibiotic treatment. The small intestine is the primary site of colonization and is followed by a transition to the colon over time, without dissemination to other tissues. Our model recapitulates the disease dynamics of the metastatic K. pneumoniae strains that are able to disseminate from the gastrointestinal tract to other sterile sites. Colonization is associated with mild to moderate histopathology, no significant inflammation, and no effect on the richness of the microbiome. Our model sums up the clinical scenario in which antibiotic treatment disturbs the colonization of K. pneumoniae and results in dissemination to other tissues. Finally, we establish that the capsule polysaccharide is necessary for the colonization of the large intestine, whereas the type VI secretion system contributes to colonization across the gastrointestinal tract. IMPORTANCE Klebsiella pneumoniae is one of the pathogens that is sweeping the world in the antibiotic resistance pandemic. Klebsiella colonizes the nasopharynx and the gut of healthy subjects in an asymptomatic manner, making gut colonization a requisite for infection. This makes it essential to understand the gastrointestinal carriage in preventing Klebsiella infections. Current research models rely on the perturbation of the gut microbiome by antibiotics, resulting in an invasive infection. Here, we report a new model of K. pneumoniae gut colonization that recapitulates key features of the asymptomatic human gastrointestinal tract colonization. In our model, there is no need to disturb the microbiota to achieve stable colonization, and there is no dissemination to other tissues. Our model sums up the clinical scenario in which antibiotic treatment triggers invasive infection. We envision that our model will be an excellent platform upon which to investigate factors enhancing colonization and invasive infections and to test therapeutics to eliminate Klebsiella asymptomatic colonization.
Klebsiella pneumoniae is a leading cause of nosocomial and community acquired infections, making K. pneumoniae the pathogen that is associated with the second largest number of deaths attributed to any antibiotic resistant infection. K. pneumoniae colonizes the nasopharynx and the gastrointestinal tract in an asymptomatic manner without dissemination to other tissues. Importantly, gastrointestinal colonization is a requisite for infection. Our understanding of K. pneumoniae colonization is still based on interrogating mouse models in which animals are pretreated with antibiotics to disturb the colonization resistance imposed by the gut microbiome. In these models, infections disseminate to other tissues. Here, we report a murine model to allow for the study of the gastrointestinal colonization of K. pneumoniae without tissue dissemination. Hypervirulent and antibiotic resistant strains stably colonize the gastrointestinal tract of in an inbred mouse population without antibiotic treatment. The small intestine is the primary site of colonization and is followed by a transition to the colon over time, without dissemination to other tissues. Our model recapitulates the disease dynamics of the metastatic K. pneumoniae strains that are able to disseminate from the gastrointestinal tract to other sterile sites. Colonization is associated with mild to moderate histopathology, no significant inflammation, and no effect on the richness of the microbiome. Our model sums up the clinical scenario in which antibiotic treatment disturbs the colonization of K. pneumoniae and results in dissemination to other tissues. Finally, we establish that the capsule polysaccharide is necessary for the colonization of the large intestine, whereas the type VI secretion system contributes to colonization across the gastrointestinal tract. IMPORTANCE Klebsiella pneumoniae is one of the pathogens that is sweeping the world in the antibiotic resistance pandemic. Klebsiella colonizes the nasopharynx and the gut of healthy subjects in an asymptomatic manner, making gut colonization a requisite for infection. This makes it essential to understand the gastrointestinal carriage in preventing Klebsiella infections. Current research models rely on the perturbation of the gut microbiome by antibiotics, resulting in an invasive infection. Here, we report a new model of K. pneumoniae gut colonization that recapitulates key features of the asymptomatic human gastrointestinal tract colonization. In our model, there is no need to disturb the microbiota to achieve stable colonization, and there is no dissemination to other tissues. Our model sums up the clinical scenario in which antibiotic treatment triggers invasive infection. We envision that our model will be an excellent platform upon which to investigate factors enhancing colonization and invasive infections and to test therapeutics to eliminate Klebsiella asymptomatic colonization.
Author Dumigan, Amy
Hancock, Steven J.
McMullan, Ronan
Sa-Pessoa, Joana
Campbell, Eric L.
Bengoechea, Jose A.
Calderon-Gonzalez, Ricardo
Lee, Alix
Lopez-Campos, Guillermo
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Copyright Copyright © 2023 Calderon-Gonzalez et al.
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M~E
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Issue 1
Keywords type VI secretion system
capsule polysaccharide
Klebsiella pneumoniae
gut colonization
Language English
License This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. https://creativecommons.org/licenses/by/4.0
This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
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The authors declare no conflict of interest.
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Snippet Klebsiella pneumoniae is one of the pathogens that is sweeping the world in the antibiotic resistance pandemic. Klebsiella colonizes the nasopharynx and the...
Klebsiella pneumoniae is a leading cause of nosocomial and community acquired infections, making K. pneumoniae the pathogen that is associated with the second...
Klebsiella pneumoniae is a leading cause of nosocomial and community acquired infections, making K. pneumoniae the pathogen that is associated with the second...
ABSTRACT Klebsiella pneumoniae is a leading cause of nosocomial and community acquired infections, making K. pneumoniae the pathogen that is associated with...
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SubjectTerms Animals
Anti-Bacterial Agents - pharmacology
capsule polysaccharide
Gastrointestinal Tract - pathology
gut colonization
Host-Microbial Interactions
Humans
Inflammation
Klebsiella Infections - epidemiology
Klebsiella pneumoniae
Mice
Research Article
type VI secretion system
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Title Modelling the Gastrointestinal Carriage of Klebsiella pneumoniae Infections
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