Brucella melitensis Wzm/Wzt System: Changes in the Bacterial Envelope Lead to Improved Rev1Δwzm Vaccine Properties

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Fältnamn	Indikatorer	Metadata
000		04824naa a2200481 4500
001		oai:DiVA.org:umu-198334
003		SwePub
008		220802s2022 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
024	7	a https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1983342 URI
024	7	a https://doi.org/10.3389/fmicb.2022.9084952 DOI
040		a (SwePub)umu
041		a engb eng
042		9 SwePub
072	7	a ref2 swepub-contenttype
072	7	a art2 swepub-publicationtype
100	1	a Mena-Bueno, Sarau Animal Health Department, Instituto de Agrobiotecnología (IdAB, CSIC-Gobierno de Navarra), Pamplona, Spain; Agronomy, Biotecnology and Food Department, Universidad Pública de Navarra (UPNA), Pamplona, Spain4 aut
245	1 0	a Brucella melitensis Wzm/Wzt System: Changes in the Bacterial Envelope Lead to Improved Rev1Δwzm Vaccine Properties
264		c 2022-07-04
264	1	b Frontiers Media S.A.c 2022
338		a electronic2 rdacarrier
520		a The lipopolysaccharide (LPS) O-polysaccharide (O-PS) is the main virulence factor in Brucella. After synthesis in the cytoplasmic membrane, O-PS is exported to the periplasm by the Wzm/Wzt system, where it is assembled into a LPS. This translocation also engages a bactoprenol carrier required for further biosynthesis pathways, such as cell wall biogenesis. Targeting O-PS export by blockage holds great potential for vaccine development, but little is known about the biological implications of each Wzm/Wzt moiety. To improve this knowledge and to elucidate its potential application as a vaccine, we constructed and studied wzm/wzt single- and double-deletion mutants, using the attenuated strain Brucella melitensis Rev1 as the parental strain. This allowed us to describe the composition of Brucella peptidoglycan for the first time. We observed that these mutants lack external O-PS yet trigger changes in genetic transcription and in phenotypic properties associated with the outer membrane and cell wall. The three mutants are highly attenuated; unexpectedly, Rev1Δwzm also excels as an immunogenic and effective vaccine against B. melitensis and Brucella ovis in mice, revealing that low persistence is not at odds with efficacy. Rev1Δwzm is attenuated in BeWo trophoblasts, does not infect mouse placentas, and is safe in pregnant ewes. Overall, these attributes and the minimal serological interference induced in sheep make Rev1Δwzm a highly promising vaccine candidate.
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Medicinsk bioteknologix Medicinsk bioteknologi0 (SwePub)304012 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Medical Biotechnologyx Medical Biotechnology0 (SwePub)304012 hsv//eng
650	7	a NATURVETENSKAPx Biologix Mikrobiologi0 (SwePub)106062 hsv//swe
650	7	a NATURAL SCIENCESx Biological Sciencesx Microbiology0 (SwePub)106062 hsv//eng
653		a Brucella envelope
653		a lipopolysaccharide
653		a pregnant mice
653		a pregnant sheep
653		a Rev1Δwzm vaccine
653		a Wzm/Wzt system
700	1	a Poveda-Urkixo, Iratiu Animal Health Department, Instituto de Agrobiotecnología (IdAB, CSIC-Gobierno de Navarra), Pamplona, Spain4 aut
700	1	a Irazoki, Oihaneu Umeå universitet,Molekylär Infektionsmedicin, Sverige (MIMS),Umeå Centre for Microbial Research (UCMR),Institutionen för molekylärbiologi (Medicinska fakulteten)4 aut0 (Swepub:umu)oiir0001
700	1	a Palacios, Leyreu Animal Health Department, Instituto de Agrobiotecnología (IdAB, CSIC-Gobierno de Navarra), Pamplona, Spain4 aut
700	1	a Cava, Felipeu Umeå universitet,Molekylär Infektionsmedicin, Sverige (MIMS),Umeå Centre for Microbial Research (UCMR),Institutionen för molekylärbiologi (Medicinska fakulteten)4 aut0 (Swepub:umu)feca0003
700	1	a Zabalza-Baranguá, Anau Animal Health Department, Instituto de Agrobiotecnología (IdAB, CSIC-Gobierno de Navarra), Pamplona, Spain4 aut
700	1	a Grilló, María Jesúsu Animal Health Department, Instituto de Agrobiotecnología (IdAB, CSIC-Gobierno de Navarra), Pamplona, Spain4 aut
710	2	a Animal Health Department, Instituto de Agrobiotecnología (IdAB, CSIC-Gobierno de Navarra), Pamplona, Spain; Agronomy, Biotecnology and Food Department, Universidad Pública de Navarra (UPNA), Pamplona, Spainb Animal Health Department, Instituto de Agrobiotecnología (IdAB, CSIC-Gobierno de Navarra), Pamplona, Spain4 org
773	0	t Frontiers in Microbiologyd : Frontiers Media S.A.g 13q 13x 1664-302X
856	4	u https://doi.org/10.3389/fmicb.2022.908495y Fulltext
856	4	u https://umu.diva-portal.org/smash/get/diva2:1685289/FULLTEXT01.pdfx primaryx Raw objecty fulltext:print
856	4 8	u https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-198334
856	4 8	u https://doi.org/10.3389/fmicb.2022.908495

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