<named-content content-type="genus-species">Acinetobacter baumannii</named-content> Targets Human Carcinoembryonic Antigen-Related Cell Adhesion Molecules (CEACAMs) for Invasion of Pneumocytes

ABSTRACT Multidrug-resistant Acinetobacter baumannii is regarded as a life-threatening pathogen mainly associated with nosocomial and community-acquired pneumonia. Here, we show that A. baumannii can bind the human carcinoembryonic antigen-related cell adhesion molecule (CEACAM) receptors CEACAM1, C...

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Autores principales:	Cecilia Ambrosi, Daniela Scribano, Meysam Sarshar, Carlo Zagaglia, Bernhard B. Singer, Anna Teresa Palamara
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Acinetobacter baumannii carcinoembryonic antigen‐related cell adhesion molecules bacterial adhesion/invasion MAPKs Rubicon Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/6348f27852a045c4b3c56de968a787e5
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spelling	oai:doaj.org-article:6348f27852a045c4b3c56de968a787e52021-12-02T18:44:44Z<named-content content-type="genus-species">Acinetobacter baumannii</named-content> Targets Human Carcinoembryonic Antigen-Related Cell Adhesion Molecules (CEACAMs) for Invasion of Pneumocytes10.1128/mSystems.00604-202379-5077https://doaj.org/article/6348f27852a045c4b3c56de968a787e52020-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSystems.00604-20https://doaj.org/toc/2379-5077ABSTRACT Multidrug-resistant Acinetobacter baumannii is regarded as a life-threatening pathogen mainly associated with nosocomial and community-acquired pneumonia. Here, we show that A. baumannii can bind the human carcinoembryonic antigen-related cell adhesion molecule (CEACAM) receptors CEACAM1, CEACAM5, and CEACAM6. This specific interaction enhances A. baumannii internalization in membrane-bound vacuoles, promptly decorated with Rab5, Rab7, and lipidated microtubule-associated protein light chain 3 (LC3). Dissecting intracellular signaling pathways revealed that infected pneumocytes trigger interleukin-8 (IL-8) secretion via the extracellular signal-regulated kinase (ERK)1/2 and nuclear factor-kappa B (NF-κB) signaling pathways for A. baumannii clearance. However, in CEACAM1-L-expressing cells, IL-8 secretion lasts only 24 h, possibly due to an A. baumannii-dependent effect on the CEACAM1-L intracellular domain. Conversely, the glycosylphosphatidylinositol-anchored CEACAM5 and CEACAM6 activate the c-Jun NH2-terminal kinase (JNK)1/2-Rubicon-NOX2 pathway, suggestive of LC3-associated phagocytosis. Overall, our data show for the first time novel mechanisms of adhesion to and invasion of pneumocytes by A. baumannii via CEACAM-dependent signaling pathways that eventually lead to bacterial killing. These findings suggest that CEACAM upregulation could put patients at increased risk of lower respiratory tract infection by A. baumannii. IMPORTANCE This work shows for the first time that Acinetobacter baumannii binds to carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), CEACAM5, and CEACAM6. This binding significantly enhances A. baumannii internalization within alveolar host cell epithelia. Intracellular trafficking involves typical Rab5 and Rab7 vacuolar proteins as well as light chain 3 (LC3) and slowly progresses to bacterial killing by endosome acidification. CEACAM engagement by A. baumannii leads to distinct and specific downstream signaling pathways. The CEACAM1 pathway finely tunes interleukin-8 (IL-8) secretion, whereas CEACAM5 and CEACAM6 mediate LC3-associated phagocytosis. The present study provides new insights into A. baumannii-host interactions and could represent a promising therapeutic strategy to reduce pulmonary infections caused by this pathogen.Cecilia AmbrosiDaniela ScribanoMeysam SarsharCarlo ZagagliaBernhard B. SingerAnna Teresa PalamaraAmerican Society for MicrobiologyarticleAcinetobacter baumanniicarcinoembryonic antigen‐related cell adhesion moleculesbacterial adhesion/invasionMAPKsRubiconMicrobiologyQR1-502ENmSystems, Vol 5, Iss 6 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Acinetobacter baumannii carcinoembryonic antigen‐related cell adhesion molecules bacterial adhesion/invasion MAPKs Rubicon Microbiology QR1-502
spellingShingle	Acinetobacter baumannii carcinoembryonic antigen‐related cell adhesion molecules bacterial adhesion/invasion MAPKs Rubicon Microbiology QR1-502 Cecilia Ambrosi Daniela Scribano Meysam Sarshar Carlo Zagaglia Bernhard B. Singer Anna Teresa Palamara <named-content content-type="genus-species">Acinetobacter baumannii</named-content> Targets Human Carcinoembryonic Antigen-Related Cell Adhesion Molecules (CEACAMs) for Invasion of Pneumocytes
description	ABSTRACT Multidrug-resistant Acinetobacter baumannii is regarded as a life-threatening pathogen mainly associated with nosocomial and community-acquired pneumonia. Here, we show that A. baumannii can bind the human carcinoembryonic antigen-related cell adhesion molecule (CEACAM) receptors CEACAM1, CEACAM5, and CEACAM6. This specific interaction enhances A. baumannii internalization in membrane-bound vacuoles, promptly decorated with Rab5, Rab7, and lipidated microtubule-associated protein light chain 3 (LC3). Dissecting intracellular signaling pathways revealed that infected pneumocytes trigger interleukin-8 (IL-8) secretion via the extracellular signal-regulated kinase (ERK)1/2 and nuclear factor-kappa B (NF-κB) signaling pathways for A. baumannii clearance. However, in CEACAM1-L-expressing cells, IL-8 secretion lasts only 24 h, possibly due to an A. baumannii-dependent effect on the CEACAM1-L intracellular domain. Conversely, the glycosylphosphatidylinositol-anchored CEACAM5 and CEACAM6 activate the c-Jun NH2-terminal kinase (JNK)1/2-Rubicon-NOX2 pathway, suggestive of LC3-associated phagocytosis. Overall, our data show for the first time novel mechanisms of adhesion to and invasion of pneumocytes by A. baumannii via CEACAM-dependent signaling pathways that eventually lead to bacterial killing. These findings suggest that CEACAM upregulation could put patients at increased risk of lower respiratory tract infection by A. baumannii. IMPORTANCE This work shows for the first time that Acinetobacter baumannii binds to carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), CEACAM5, and CEACAM6. This binding significantly enhances A. baumannii internalization within alveolar host cell epithelia. Intracellular trafficking involves typical Rab5 and Rab7 vacuolar proteins as well as light chain 3 (LC3) and slowly progresses to bacterial killing by endosome acidification. CEACAM engagement by A. baumannii leads to distinct and specific downstream signaling pathways. The CEACAM1 pathway finely tunes interleukin-8 (IL-8) secretion, whereas CEACAM5 and CEACAM6 mediate LC3-associated phagocytosis. The present study provides new insights into A. baumannii-host interactions and could represent a promising therapeutic strategy to reduce pulmonary infections caused by this pathogen.
format	article
author	Cecilia Ambrosi Daniela Scribano Meysam Sarshar Carlo Zagaglia Bernhard B. Singer Anna Teresa Palamara
author_facet	Cecilia Ambrosi Daniela Scribano Meysam Sarshar Carlo Zagaglia Bernhard B. Singer Anna Teresa Palamara
author_sort	Cecilia Ambrosi
title	<named-content content-type="genus-species">Acinetobacter baumannii</named-content> Targets Human Carcinoembryonic Antigen-Related Cell Adhesion Molecules (CEACAMs) for Invasion of Pneumocytes
title_short	<named-content content-type="genus-species">Acinetobacter baumannii</named-content> Targets Human Carcinoembryonic Antigen-Related Cell Adhesion Molecules (CEACAMs) for Invasion of Pneumocytes
title_full	<named-content content-type="genus-species">Acinetobacter baumannii</named-content> Targets Human Carcinoembryonic Antigen-Related Cell Adhesion Molecules (CEACAMs) for Invasion of Pneumocytes
title_fullStr	<named-content content-type="genus-species">Acinetobacter baumannii</named-content> Targets Human Carcinoembryonic Antigen-Related Cell Adhesion Molecules (CEACAMs) for Invasion of Pneumocytes
title_full_unstemmed	<named-content content-type="genus-species">Acinetobacter baumannii</named-content> Targets Human Carcinoembryonic Antigen-Related Cell Adhesion Molecules (CEACAMs) for Invasion of Pneumocytes
title_sort	<named-content content-type="genus-species">acinetobacter baumannii</named-content> targets human carcinoembryonic antigen-related cell adhesion molecules (ceacams) for invasion of pneumocytes
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/6348f27852a045c4b3c56de968a787e5
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<named-content content-type="genus-species">Acinetobacter baumannii</named-content> Targets Human Carcinoembryonic Antigen-Related Cell Adhesion Molecules (CEACAMs) for Invasion of Pneumocytes

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