Hypermucoviscous carbapenem-resistant Klebsiella pneumoniae strains from sequence type 25 infect human intestinal epithelial cells and stimulate inflammatory response

SAHA, SUDEB; DENTICE MAIDANA, STEFANIA; ELEAN, MARIANO; FUKUYAMA, KOHTARO; VARGAS, JUAN MARTIN; SERDA, RODRIGO; JURE, MARÍA ÁNGELA; KITAZAWA, HARUKI; JULIO VILLENA

Hamburg

Congreso; 10th Congress of European Microbiologists - FEMS Congress 2023; 2023

FEMS

The prevalence of hypermucoviscous carbapenem-resistant Klebsiella pneumoniae with sequence type 25 (ST25) is increasing in South America. In this work, the infectivity and the inflammatory response triggered two K. pneumoniae ST25 strains (LABACER01 and LABACER27) were evaluated in human intestinal epithelial cells. Caco-2 cells (7×105 cells/well) were challenged with LABACER01 or LABACER27 (104 cells/well) and at different hours pots-infection (2, 6 and 12) the cytotoxic effect, adhesion, and invasion rate, as well as the expression of tight junctions and inflammatory cytokines were investigated. LPS challenge was used as control for inflammation. LPS and both K. pneumoniae strains significantly reduced cell viability and increased LDH release, indicating cell damage. However, the effects of bacteria were lower than LPS (p < 0.05). No differences in cell viability or LDH activity were detected between the LABACER strains. Both K. pneumoniae strains adhered to and invaded Caco-2 cells, with no significant differences between them (p < 0.05). LPS and LABACER strains significantly reduced the expression of occludin, ZO-1, and claudin, increased the expression of the inflammatory factors COX-2, iNOS, and enhanced the mRNA and protein levels of TNF-α, IL-6, MCP-1, and IL-8. LABACER01 and LABACER27 showed a lower ability to stimulate inflammatory response than LPS and no significant differences were observed between the two bacteria. Here, the virulence and inflammatory profile of hypermucoviscous carbapenem-resistant K. pneumoniae ST25 was explored for the first time in human intestinal epithelial cells. Results expand the knowledge of the biology of these emerging multiresistant K. pneumoniae clones.