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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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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, br. 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 i Yousef Abu Kwaik. "An Indispensable Role for the MavE Effector of in Lysosomal Evasion." mBio 12, br. 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, i sur.. An Indispensable Role for the MavE Effector of in Lysosomal Evasion. mBio [Internet]. 09.02.2021. [pristupljeno 18.03.2025.];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, br. 1, Veljača 2021. [Online]. Dostupno na: https://urn.nsk.hr/urn:nbn:hr:184:265093. [Citirano: 18.03.2025.]

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Naslov (engleski)An Indispensable Role for the MavE Effector of in Lysosomal Evasion
AutorBethany Vaughn
AutorKevin Voth
AutorChristopher T. Price
AutorSnake Jones
AutorMateja Ožanič
AutorMarina Šantić
AutorMiroslaw Cygler
AutorYousef Abu Kwaik
Autorova ustanovaSveučilište u Rijeci
Medicinski fakultet
(Katedra za mikrobiologiju i parazitologiju)
Znanstveno / umjetničko
područje, polje i grana		BIOMEDICINA I ZDRAVSTVO
Kliničke medicinske znanosti
Medicinska mikrobiologija
Sažetak (engleski)
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... Više 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. Sakrij dio sažetka
Ključne riječi (engleski)
Jezikengleski
Vrsta publikacijeZnanstveni rad - Izvorni znanstveni rad
Status objaveObjavljen
Vrsta recenzijeRecenziran - međunarodna recenzija
Verzija publikacijeZavršna verzija rukopisa prihvaćena za objavljivanje (postprint)
Naslov časopisamBio
Brojčani podacivol. 12, br. 1, 03458-20
e-ISSN2150-7511
DOIhttps://doi.org/10.1128/mBio.03458-20
URN:NBNurn:nbn:hr:184:265093
Datum objave publikacije2021-02-09
ProjektŠifra: IP-2016-06-9003
Naziv (hrvatski): Uloga unutarstaničnog života Francisella tularensis u patogenezi eksperimentalne tularemije
Kratica: FRANCYCLE
Voditelj: Marina Šantić
Pravna nadležnost: Hrvatska
Financijer: HRZZ
Linija financiranja: IP
URL dokumentahttps://mbio.asm.org/content/12/1/e03458-20
Vrsta resursaTekst
Prava pristupaOtvoreni pristup
Uvjeti korištenjaIkona licence Imenovanje 4.0 međunarodna (CC BY 4.0)
Datum i vrijeme pohrane2021-02-21 21:46:24
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