Encapsulin protein MAV2054 enhances Mycobacterium avium virulence by promoting Cdc42-dependent epithelial cell invasion

Mycobacterium avium complex (MAC) organisms are widespread environmental pathogens associated with chronic pulmonary infections. Although M. avium is known to invade epithelial cells, the molecular mechanisms underlying this process remain incompletely understood. In this study, we identified a nove...

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Published in:The journal of microbiology Vol. 63; no. 11; p. e2506008
Main Authors: Kim, Dong Ho, Jo, I Jeong, Kang, Min Ju, Kim, Yi Seol, Huong, Duyen Do Tran, Woo, Kyungho, Park, Ho-Sung, Kim, Hwa-Jung, Choi, Chul Hee
Format: Journal Article
Language:English
Published: Korea (South) 한국미생물학회 01.11.2025
Subjects:
Animals
Bacterial Adhesion
Bacterial Proteins - genetics
Bacterial Proteins - metabolism
cdc42 GTP-Binding Protein - genetics
cdc42 GTP-Binding Protein - metabolism
Cell Line
Disease Models, Animal
Epithelial Cells - microbiology
Female
Humans
Mice
Mice, Inbred BALB C
Mycobacterium avium Complex - genetics
Mycobacterium avium Complex - metabolism
Mycobacterium avium Complex - pathogenicity
Virulence
Virulence Factors - genetics
Virulence Factors - metabolism
생물학
Mycobacterium avium
MAV2054
actin cytoskeleton remodeling
encapsulin nanocompartment
ISSN:1976-3794, 1225-8873, 1976-3794
Online Access:Get full text
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Summary:Mycobacterium avium complex (MAC) organisms are widespread environmental pathogens associated with chronic pulmonary infections. Although M. avium is known to invade epithelial cells, the molecular mechanisms underlying this process remain incompletely understood. In this study, we identified a novel role for MAVRS09815 (formerly MAV2054), a family 2A encapsulin nanocompartment shell protein, in mediating bacterial adhesion, epithelial cell invasion, and in vivo virulence. We engineered a recombinant M. smegmatis strain expressing MAV2054 (Ms_2054) and an M. avium MAV2054 deletion mutant (Δ2054). Ms_2054 exhibited enhanced epithelial invasion, whereas Δ2054 showed reduced intracellular survival. Recombinant MAV2054 protein was bound directly to human epithelial cells in a dose-dependent manner. Pretreatment of host cells with cytochalasin D or vinblastine significantly inhibited bacterial internalization, indicating that MAV2054-mediated invasion is cytoskeleton-dependent. Confocal and scanning electron microscopy revealed MAV2054-dependent membrane rearrangements during infection. Pull-down assays demonstrated that MAV2054 activates Cdc42, a key regulator of actin polymerization, with reduced activation observed in Δ2054-infected cells. In a murine intratracheal infection model, the Δ2054 exhibited significantly reduced bacterial burdens and lung inflammation compared to the wild type. These findings demonstrate that MAV2054 enhances M. avium virulence by promoting epithelial cell invasion through Cdc42-dependent cytoskeletal remodeling. This study reveals a previously unrecognized role for an encapsulin-like protein in host-pathogen interactions and highlights its potential as a therapeutic target in MAC infections.
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ISSN:1976-3794
1225-8873
1976-3794
DOI:10.71150/jm.2506008