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Scientific paper - Original scientific paper
An Indispensable Role for the MavE Effector of in Lysosomal Evasion
mBio, 12 (2021), 1; 03458-20. https://doi.org/10.1128/mBio.03458-20
Vaughn, Bethany; Voth, Kevin; Price, Christopher T.; Jones, Snake; Ožanič, Mateja; Šantić, Marina; Cygler, Miroslaw; Abu Kwaik, Yousef

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Institutional repository: Repository of the University of Rijeka, Faculty of Medicine

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Vaughn, B., Voth, K., Price, C. T., Jones, S., Ožanič, M., Šantić, M. ... Abu Kwaik, Y. (2021). An Indispensable Role for the MavE Effector of in Lysosomal Evasion. mBio, 12. (1). doi: 10.1128/mBio.03458-20

Vaughn, Bethany, et al. "An Indispensable Role for the MavE Effector of in Lysosomal Evasion." mBio, vol. 12, no. 1, 2021. https://doi.org/10.1128/mBio.03458-20

Vaughn, Bethany, Kevin Voth, Christopher T. Price, Snake Jones, Mateja Ožanič, Marina Šantić, Miroslaw Cygler and Yousef Abu Kwaik. "An Indispensable Role for the MavE Effector of in Lysosomal Evasion." mBio 12, no. 1 (2021). https://doi.org/10.1128/mBio.03458-20

Vaughn, B., et al. (2021) 'An Indispensable Role for the MavE Effector of in Lysosomal Evasion', mBio, 12(1). doi: 10.1128/mBio.03458-20

Vaughn B, Voth K, Price CT, Jones S, Ožanič M, Šantić M, and sur.. An Indispensable Role for the MavE Effector of in Lysosomal Evasion. mBio [Internet]. 2021 February 09 [cited 2025 March 14];12(1). doi: 10.1128/mBio.03458-20

B. Vaughn, et al., "An Indispensable Role for the MavE Effector of in Lysosomal Evasion", mBio, vol. 12, no. 1, February 2021. [Online]. Available at: https://urn.nsk.hr/urn:nbn:hr:184:265093. [Accessed: 14 March 2025]

Metadata
Title (english)An Indispensable Role for the MavE Effector of in Lysosomal Evasion
AuthorBethany Vaughn
AuthorKevin Voth
AuthorChristopher T. Price
AuthorSnake Jones
AuthorMateja Ožanič
AuthorMarina Šantić
AuthorMiroslaw Cygler
AuthorYousef Abu Kwaik
Author's institutionUniversity of Rijeka
Faculty of Medicine
(Department of Microbiology and Parasitology)
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Clinical Medical Sciences
Medical Microbiology
Abstract (english)
ABSTRACT Diversion of the -containing vacuole (LCV) from the host endosomal-lysosomal degradation pathway is one of the main virulence features essential for manifestation of Legionnaires’ pneumonia. Many of the ∼350 Dot/Icm-injected effectors identified in have been shown to interfere with various host pathways and processes, but no effector has ever... More been identified to be indispensable for lysosomal evasion. While most single effector mutants of do not exhibit a defective phenotype within macrophages, we show that the MavE effector is essential for intracellular growth of in human monocyte-derived macrophages (hMDMs) and amoebae and for intrapulmonary proliferation in mice. The null mutant fails to remodel the LCV with endoplasmic reticulum (ER)-derived vesicles and is trafficked to the lysosomes where it is degraded, similar to formalin-killed bacteria. During infection of hMDMs, the MavE effector localizes to the poles of the LCV membrane. The crystal structure of MavE, resolved to 1.8 Å, reveals a C-terminal transmembrane helix, three copies of tyrosine-based sorting motifs, and an NPxY eukaryotic motif, which binds phosphotyrosine-binding domains present on signaling and adaptor eukaryotic proteins. Two point mutations within the NPxY motif result in attenuation of in both hMDMs and amoeba. The substitution defects of P and D are associated with failure of vacuoles harboring the mutant to be remodeled by the ER and results in fusion of the vacuole to the lysosomes leading to bacterial degradation. Therefore, the MavE effector of is indispensable for phagosome biogenesis and lysosomal evasion. Intracellular proliferation of within a vacuole in human alveolar macrophages is essential for manifestation of Legionnaires’ pneumonia. Intravacuolar growth of the pathogen is totally dependent on remodeling the -containing vacuole (LCV) by the ER and on its evasion of the endosomal-lysosomal degradation pathway. The pathogen has evolved to inject ∼350 protein effectors into the host cell where they modulate various host processes, but no effector has ever been identified to be indispensable for lysosomal evasion. We show that the MavE effector localizes to the poles of the LCV membrane and is essential for lysosomal evasion and intracellular growth of and for intrapulmonary proliferation in mice. The crystal structure of MavE shows an NPxY eukaryotic motif essential for ER-mediated remodeling and lysosomal evasion by the LCV. Therefore, the MavE effector of is indispensable for phagosome biogenesis and lysosomal evasion. Less
Keywords (english)
Languageenglish
Publication typeScientific paper - Original scientific paper
Publication statusPublished
Peer reviewPeer review - international
Publication versionAccepted version
Journal titlemBio
Numberingvol. 12, no. 1, 03458-20
e-ISSN2150-7511
DOIhttps://doi.org/10.1128/mBio.03458-20
URN:NBNurn:nbn:hr:184:265093
Publication2021-02-09
ProjectNumber: IP-2016-06-9003
Title (croatian): Uloga unutarstaničnog života Francisella tularensis u patogenezi eksperimentalne tularemije
Acronym: FRANCYCLE
Leader: Marina Šantić
Jurisdiction: Croatia
Funding stream: IP
Document URLhttps://mbio.asm.org/content/12/1/e03458-20
Type of resourceText
Access conditionsOpen access
Terms of useLicence Attribution 4.0 International (CC BY 4.0) icon
Created on2021-02-21 21:46:24
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