000063040 001__ 63040
000063040 005__ 20190709135519.0
000063040 0247_ $$2doi$$a10.3389/fcimb.2017.00186
000063040 0248_ $$2sideral$$a101727
000063040 037__ $$aART-2017-101727
000063040 041__ $$aeng
000063040 100__ $$aAbdou, E.
000063040 245__ $$aRegA plays a key role in oxygen-dependent establishment of persistence and in isocitrate lyase activity, a critical determinant of in vivo Brucella suis pathogenicity
000063040 260__ $$c2017
000063040 5060_ $$aAccess copy available to the general public$$fUnrestricted
000063040 5203_ $$aFor aerobic human pathogens, adaptation to hypoxia is a critical factor for the establishment of persistent infections, as oxygen availability is low inside the host. The two-component system RegB/A of Brucella suis plays a central role in the control of respiratory systems adapted to oxygen deficiency, and in persistence in vivo. Using an original “in vitro model of persistence” consisting in gradual oxygen depletion, we compared transcriptomes and proteomes of wild-type and ¿regA strains to identify the RegA-regulon potentially involved in the set-up of persistence. Consecutive to oxygen consumption resulting in growth arrest, 12% of the genes in B. suis were potentially controlled directly or indirectly by RegA, among which numerous transcriptional regulators were up-regulated. In contrast, genes or proteins involved in envelope biogenesis and in cellular division were repressed, suggesting a possible role for RegA in the set-up of a non-proliferative persistence state. Importantly, the greatest number of the RegA-repressed genes and proteins, including aceA encoding the functional IsoCitrate Lyase (ICL), were involved in energy production. A potential consequence of this RegA impact may be the slowing-down of the central metabolism as B. suis progressively enters into persistence. Moreover, ICL is an essential determinant of pathogenesis and long-term interactions with the host, as demonstrated by the strict dependence of B. suis on ICL activity for multiplication and persistence during in vivo infection. RegA regulates gene or protein expression of all functional groups, which is why RegA is a key regulator of B. suis in adaptation to oxygen depletion. This function may contribute to the constraint of bacterial growth, typical of chronic infection. Oxygen-dependent activation of two-component systems that control persistence regulons, shared by several aerobic human pathogens, has not been studied in Brucella sp. before. This work therefore contributes significantly to the unraveling of persistence mechanisms in this important zoonotic pathogen.
000063040 536__ $$9info:eu-repo/grantAgreement/ES/INIA/RTA2013-00065-C02-01
000063040 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000063040 590__ $$a3.52$$b2017
000063040 591__ $$aMICROBIOLOGY$$b40 / 125 = 0.32$$c2017$$dQ2$$eT1
000063040 591__ $$aIMMUNOLOGY$$b64 / 155 = 0.413$$c2017$$dQ2$$eT2
000063040 592__ $$a1.703$$b2017
000063040 593__ $$aMedicine (miscellaneous)$$c2017$$dQ1
000063040 593__ $$aInfectious Diseases$$c2017$$dQ1
000063040 593__ $$aMicrobiology (medical)$$c2017$$dQ1
000063040 593__ $$aMicrobiology$$c2017$$dQ1
000063040 593__ $$aImmunology$$c2017$$dQ2
000063040 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000063040 700__ $$0(orcid)0000-0002-5490-5177$$aJiménez de Bagüés, M.P.
000063040 700__ $$aMartínez-Abadía, I.
000063040 700__ $$aOuahrani-Bettache, S.
000063040 700__ $$aPantesco, V.
000063040 700__ $$aOcchialini, A.
000063040 700__ $$aAl Dahouk, S.
000063040 700__ $$aKöhler, S.
000063040 700__ $$aJubier-Maurin, V.
000063040 773__ $$g7 (2017), 186 [19 pp]$$tFrontiers in cellular and infection microbiology$$x2235-2988
000063040 8564_ $$s341294$$uhttps://zaguan.unizar.es/record/63040/files/texto_completo.pdf$$yVersión publicada
000063040 8564_ $$s12083$$uhttps://zaguan.unizar.es/record/63040/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000063040 909CO $$ooai:zaguan.unizar.es:63040$$particulos$$pdriver
000063040 951__ $$a2019-07-09-11:56:38
000063040 980__ $$aARTICLE