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Listeria adhesion protein orchestrates caveolae-mediated apical junctional remodeling of epithelial barrier for Listeria monocytogenes translocation.
Drolia, Rishi; Bryant, Donald B; Tenguria, Shivendra; Jules-Culver, Zuri A; Thind, Jessie; Amelunke, Breanna; Liu, Dongqi; Gallina, Nicholas L F; Mishra, Krishna K; Samaddar, Manalee; Sawale, Manoj R; Mishra, Dharmendra K; Cox, Abigail D; Bhunia, Arun K.
Afiliação
  • Drolia R; Department of Food Science, Molecular Food Microbiology Laboratory, Purdue University, West Lafayette, Indiana, USA.
  • Bryant DB; Department of Biological Science, Old Dominion University, Norfolk, Virginia, USA.
  • Tenguria S; Department of Biological Science, Eastern Kentucky University, Richmond, Kentucky, USA.
  • Jules-Culver ZA; Purdue Institute of Inflammation, Immunology, and Infectious Disease, Purdue University, West Lafayette, Indiana, USA.
  • Thind J; Department of Biological Science, Eastern Kentucky University, Richmond, Kentucky, USA.
  • Amelunke B; Department of Food Science, Molecular Food Microbiology Laboratory, Purdue University, West Lafayette, Indiana, USA.
  • Liu D; Purdue Institute of Inflammation, Immunology, and Infectious Disease, Purdue University, West Lafayette, Indiana, USA.
  • Gallina NLF; Department of Biological Science, Old Dominion University, Norfolk, Virginia, USA.
  • Mishra KK; Department of Biological Science, Eastern Kentucky University, Richmond, Kentucky, USA.
  • Samaddar M; Department of Biological Science, Eastern Kentucky University, Richmond, Kentucky, USA.
  • Sawale MR; Department of Food Science, Molecular Food Microbiology Laboratory, Purdue University, West Lafayette, Indiana, USA.
  • Mishra DK; Purdue Institute of Inflammation, Immunology, and Infectious Disease, Purdue University, West Lafayette, Indiana, USA.
  • Cox AD; Department of Food Science, Molecular Food Microbiology Laboratory, Purdue University, West Lafayette, Indiana, USA.
  • Bhunia AK; Purdue Institute of Inflammation, Immunology, and Infectious Disease, Purdue University, West Lafayette, Indiana, USA.
mBio ; 15(3): e0282123, 2024 Mar 13.
Article em En | MEDLINE | ID: mdl-38376160
ABSTRACT
The cellular junctional architecture remodeling by Listeria adhesion protein-heat shock protein 60 (LAP-Hsp60) interaction for Listeria monocytogenes (Lm) passage through the epithelial barrier is incompletely understood. Here, using the gerbil model, permissive to internalin (Inl) A/B-mediated pathways like in humans, we demonstrate that Lm crosses the intestinal villi at 48 h post-infection. In contrast, the single isogenic (lap- or ΔinlA) or double (lap-ΔinlA) mutant strains show significant defects. LAP promotes Lm translocation via endocytosis of cell-cell junctional complex in enterocytes that do not display luminal E-cadherin. In comparison, InlA facilitates Lm translocation at cells displaying apical E-cadherin during cell extrusion and mucus expulsion from goblet cells. LAP hijacks caveolar endocytosis to traffic integral junctional proteins to the early and recycling endosomes. Pharmacological inhibition in a cell line and genetic knockout of caveolin-1 in mice prevents LAP-induced intestinal permeability, junctional endocytosis, and Lm translocation. Furthermore, LAP-Hsp60-dependent tight junction remodeling is also necessary for InlA access to E-cadherin for Lm intestinal barrier crossing in InlA-permissive hosts. IMPORTANCE Listeria monocytogenes (Lm) is a foodborne pathogen with high mortality (20%-30%) and hospitalization rates (94%), particularly affecting vulnerable groups such as pregnant women, fetuses, newborns, seniors, and immunocompromised individuals. Invasive listeriosis involves Lm's internalin (InlA) protein binding to E-cadherin to breach the intestinal barrier. However, non-functional InlA variants have been identified in Lm isolates, suggesting InlA-independent pathways for translocation. Our study reveals that Listeria adhesion protein (LAP) and InlA cooperatively assist Lm entry into the gut lamina propria in a gerbil model, mimicking human listeriosis in early infection stages. LAP triggers caveolin-1-mediated endocytosis of critical junctional proteins, transporting them to early and recycling endosomes, facilitating Lm passage through enterocytes. Furthermore, LAP-Hsp60-mediated junctional protein endocytosis precedes InlA's interaction with basolateral E-cadherin, emphasizing LAP and InlA's cooperation in enhancing Lm intestinal translocation. This understanding is vital in combating the severe consequences of Lm infection, including sepsis, meningitis, encephalitis, and brain abscess.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Listeria / Listeriose / Listeria monocytogenes Limite: Animals / Female / Humans / Newborn / Pregnancy Idioma: En Revista: MBio Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Listeria / Listeriose / Listeria monocytogenes Limite: Animals / Female / Humans / Newborn / Pregnancy Idioma: En Revista: MBio Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Estados Unidos