Hypermucoviscous Carbapenem-Resistant <i>Klebsiella pneumoniae</i> ST25 Infect Human Intestinal Epithelial Cells and Induce Moderate Inflammation

<i>Klebsiella pneumoniae</i> is an opportunistic pathogen that can produce moderate and severe infections in immunosuppressed hosts. In recent years, an increase in the isolation of hypermucoviscous carbapenem-resistant <i>K. pneumoniae</i> with sequence type 25 (ST25) in hos...

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Main Authors: Stefania Dentice Maidana, Mariano Elean, Kohtaro Fukuyama, Yoshiya Imamura, Leonardo Albarracín, Sudeb Saha, Yoshihito Suda, Shoichiro Kurata, María Ángela Jure, Haruki Kitazawa, Julio Villena
Format: Article
Language:English
Published: MDPI AG 2023-05-01
Series:International Journal of Molecular Sciences
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Online Access:https://www.mdpi.com/1422-0067/24/10/8804
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author Stefania Dentice Maidana
Mariano Elean
Kohtaro Fukuyama
Yoshiya Imamura
Leonardo Albarracín
Sudeb Saha
Yoshihito Suda
Shoichiro Kurata
María Ángela Jure
Haruki Kitazawa
Julio Villena
author_facet Stefania Dentice Maidana
Mariano Elean
Kohtaro Fukuyama
Yoshiya Imamura
Leonardo Albarracín
Sudeb Saha
Yoshihito Suda
Shoichiro Kurata
María Ángela Jure
Haruki Kitazawa
Julio Villena
author_sort Stefania Dentice Maidana
collection DOAJ
description <i>Klebsiella pneumoniae</i> is an opportunistic pathogen that can produce moderate and severe infections in immunosuppressed hosts. In recent years, an increase in the isolation of hypermucoviscous carbapenem-resistant <i>K. pneumoniae</i> with sequence type 25 (ST25) in hospitals in Norwest Argentina was observed. This work aimed to study the virulence and inflammatory potential of two <i>K. pneumoniae</i> ST25 strains (LABACER01 and LABACER27) in the intestinal mucosa. The human intestinal Caco-2 cells were infected with the <i>K. pneumoniae</i> ST25 strains, and their adhesion and invasion rates and changes in the expression of tight junction and inflammatory factors genes were evaluated. ST25 strains were able to adhere and invade Caco-2 cells, reducing their viability. Furthermore, both strains reduced the expression of tight junction proteins (occludin, ZO-1, and claudin-5), altered permeability, and increased the expression of TGF-β and TLL1 and the inflammatory factors (COX-2, iNOS, MCP-1, IL-6, IL-8, and TNF-α) in Caco-2 cells. The inflammatory response induced by LABACER01 and LABACER27 was significantly lower than the one produced by LPS or other intestinal pathogens, including <i>K. pneumoniae</i> NTUH-K2044. No differences in virulence and inflammatory potential were found between LABACER01 and LABACER27. In line with these findings, no major differences between the strains were found when the comparative genomic analysis of virulence factors associated with intestinal infection/colonization was performed. This work is the first to demonstrate that hypermucoviscous carbapenem-resistant <i>K. pneumoniae</i> ST25 infects human intestinal epithelial cells and induces moderate inflammation.
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spelling doaj.art-2d5a708ddff44fe1a9384ba05ff608e12023-11-18T01:42:12ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-05-012410880410.3390/ijms24108804Hypermucoviscous Carbapenem-Resistant <i>Klebsiella pneumoniae</i> ST25 Infect Human Intestinal Epithelial Cells and Induce Moderate InflammationStefania Dentice Maidana0Mariano Elean1Kohtaro Fukuyama2Yoshiya Imamura3Leonardo Albarracín4Sudeb Saha5Yoshihito Suda6Shoichiro Kurata7María Ángela Jure8Haruki Kitazawa9Julio Villena10Laboratory of Immunobiotechnology, Reference Centre for Lactobacilli (CERELA-CONICET), Tucuman 4000, ArgentinaLaboratory of Immunobiotechnology, Reference Centre for Lactobacilli (CERELA-CONICET), Tucuman 4000, ArgentinaFood and Feed Immunology Group, Laboratory of Animal Food Function, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8577, JapanFood and Feed Immunology Group, Laboratory of Animal Food Function, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8577, JapanLaboratory of Immunobiotechnology, Reference Centre for Lactobacilli (CERELA-CONICET), Tucuman 4000, ArgentinaFood and Feed Immunology Group, Laboratory of Animal Food Function, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8577, JapanDepartment of Food, Agriculture and Environment, Miyagi University, Sendai 980-8572, JapanLaboratory of Molecular Genetics, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, JapanLaboratory of Antimicrobials, Institute of Microbiology “Luis C. Verna”, Faculty of Biochemistry, Chemistry and Pharmacy, National University of Tucuman, Tucuman 4000, ArgentinaFood and Feed Immunology Group, Laboratory of Animal Food Function, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8577, JapanLaboratory of Immunobiotechnology, Reference Centre for Lactobacilli (CERELA-CONICET), Tucuman 4000, Argentina<i>Klebsiella pneumoniae</i> is an opportunistic pathogen that can produce moderate and severe infections in immunosuppressed hosts. In recent years, an increase in the isolation of hypermucoviscous carbapenem-resistant <i>K. pneumoniae</i> with sequence type 25 (ST25) in hospitals in Norwest Argentina was observed. This work aimed to study the virulence and inflammatory potential of two <i>K. pneumoniae</i> ST25 strains (LABACER01 and LABACER27) in the intestinal mucosa. The human intestinal Caco-2 cells were infected with the <i>K. pneumoniae</i> ST25 strains, and their adhesion and invasion rates and changes in the expression of tight junction and inflammatory factors genes were evaluated. ST25 strains were able to adhere and invade Caco-2 cells, reducing their viability. Furthermore, both strains reduced the expression of tight junction proteins (occludin, ZO-1, and claudin-5), altered permeability, and increased the expression of TGF-β and TLL1 and the inflammatory factors (COX-2, iNOS, MCP-1, IL-6, IL-8, and TNF-α) in Caco-2 cells. The inflammatory response induced by LABACER01 and LABACER27 was significantly lower than the one produced by LPS or other intestinal pathogens, including <i>K. pneumoniae</i> NTUH-K2044. No differences in virulence and inflammatory potential were found between LABACER01 and LABACER27. In line with these findings, no major differences between the strains were found when the comparative genomic analysis of virulence factors associated with intestinal infection/colonization was performed. This work is the first to demonstrate that hypermucoviscous carbapenem-resistant <i>K. pneumoniae</i> ST25 infects human intestinal epithelial cells and induces moderate inflammation.https://www.mdpi.com/1422-0067/24/10/8804<i>Klebsiella pneumoniae</i>carbapenem resistantintestinal infectiongenomicsequence type 25
spellingShingle Stefania Dentice Maidana
Mariano Elean
Kohtaro Fukuyama
Yoshiya Imamura
Leonardo Albarracín
Sudeb Saha
Yoshihito Suda
Shoichiro Kurata
María Ángela Jure
Haruki Kitazawa
Julio Villena
Hypermucoviscous Carbapenem-Resistant <i>Klebsiella pneumoniae</i> ST25 Infect Human Intestinal Epithelial Cells and Induce Moderate Inflammation
International Journal of Molecular Sciences
<i>Klebsiella pneumoniae</i>
carbapenem resistant
intestinal infection
genomic
sequence type 25
title Hypermucoviscous Carbapenem-Resistant <i>Klebsiella pneumoniae</i> ST25 Infect Human Intestinal Epithelial Cells and Induce Moderate Inflammation
title_full Hypermucoviscous Carbapenem-Resistant <i>Klebsiella pneumoniae</i> ST25 Infect Human Intestinal Epithelial Cells and Induce Moderate Inflammation
title_fullStr Hypermucoviscous Carbapenem-Resistant <i>Klebsiella pneumoniae</i> ST25 Infect Human Intestinal Epithelial Cells and Induce Moderate Inflammation
title_full_unstemmed Hypermucoviscous Carbapenem-Resistant <i>Klebsiella pneumoniae</i> ST25 Infect Human Intestinal Epithelial Cells and Induce Moderate Inflammation
title_short Hypermucoviscous Carbapenem-Resistant <i>Klebsiella pneumoniae</i> ST25 Infect Human Intestinal Epithelial Cells and Induce Moderate Inflammation
title_sort hypermucoviscous carbapenem resistant i klebsiella pneumoniae i st25 infect human intestinal epithelial cells and induce moderate inflammation
topic <i>Klebsiella pneumoniae</i>
carbapenem resistant
intestinal infection
genomic
sequence type 25
url https://www.mdpi.com/1422-0067/24/10/8804
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