Acinetobacter baumannii Targets Human Carcinoembryonic Antigen-Related Cell Adhesion Molecules (CEACAMs) for Invasion of Pneumocytes

• Published in: mSystems Vol. 5; no. 6
• Main Authors: Ambrosi, Cecilia, Scribano, Daniela, Sarshar, Meysam, Zagaglia, Carlo, Singer, Bernhard B, Palamara, Anna Teresa
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 22.12.2020
• Subjects: Acinetobacter baumannii; bacterial adhesion/invasion; carcinoembryonic antigen‐related cell adhesion molecules; Host-Microbe Biology; MAPKs; Rubicon; Acinetobacter baumannii; bacterial adhesion/invasion; Rubicon; carcinoembryonic antigen‐related cell adhesion molecules; MAPKs
• ISSN: 2379-5077; 2379-5077
• DOI: 10.1128/mSystems.00604-20

Multidrug-resistant is regarded as a life-threatening pathogen mainly associated with nosocomial and community-acquired pneumonia. Here, we show that can bind the human carcinoembryonic antigen-related cell adhesion molecule (CEACAM) receptors CEACAM1, CEACAM5, and CEACAM6. This specific interaction enhances 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 clearance. However, in CEACAM1-L-expressing cells, IL-8 secretion lasts only 24 h, possibly due to an -dependent effect on the CEACAM1-L intracellular domain. Conversely, the glycosylphosphatidylinositol-anchored CEACAM5 and CEACAM6 activate the c-Jun NH -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 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 This work shows for the first time that binds to carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), CEACAM5, and CEACAM6. This binding significantly enhances 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 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 -host interactions and could represent a promising therapeutic strategy to reduce pulmonary infections caused by this pathogen.