000118916 001__ 118916 000118916 005__ 20240319081008.0 000118916 0247_ $$2doi$$a10.3389/fcimb.2022.907890 000118916 0248_ $$2sideral$$a130315 000118916 037__ $$aART-2022-130315 000118916 041__ $$aeng 000118916 100__ $$aGarcía-Morales, L. 000118916 245__ $$aThe lack of the TetR-like repressor gene BCG_2177c (Rv2160A) may help mycobacteria overcome intracellular redox stress and survive longer inside macrophages when surrounded by a lipid environment 000118916 260__ $$c2022 000118916 5060_ $$aAccess copy available to the general public$$fUnrestricted 000118916 5203_ $$aMycobacteria, like other microorganisms, survive under different environmental variations by expressing an efficient adaptive response, oriented by regulatory elements, such as transcriptional repressors of the TetR family. These repressors in mycobacteria also appear to be related to cholesterol metabolism. In this study, we have evaluated the effect of a fatty acid (oleic–palmitic–stearic)/cholesterol mixture on some phenotypic and genotypic characteristics of a tetR-mutant strain (BCG_2177c mutated gene) of M. bovis BCG, a homologous of Rv2160A of M. tuberculosis. In order to accomplish this, we have analyzed the global gene expression of this strain by RNA-seq and evaluated its neutral-lipid storage capacity and potential to infect macrophages. We have also determined the macrophage response by measuring some pro- and anti-inflammatory cytokine expressions. In comparison with wild-type microorganisms, we showed that the mutation in the BCG_2177c gene did not affect the growth of M. bovis BCG in the presence of lipids but it probably modified the structure/composition of its cell envelope. Compared to with dextrose, an overexpression of the transcriptome of the wild-type and mutant strains was observed when these mycobacteria were cultured in lipids, mainly at the exponential phase. Twelve putative intracellular redox balance maintenance genes and four others coding for putative transcriptional factors (including WhiB6 and three TetR-like) were the main elements repeatedly overexpressed when cultured in the presence of lipids. These genes belonged to the central part of what we called the “genetic lipid signature” for M. bovis BCG. We have also found that all these mycobacteria genotypic changes affected the outcome of BCG-infected macrophages, being the mutant strain most adapted to persist longer inside the host. This high persistence result was also confirmed when mutant-infected macrophages showed overexpression of the anti-inflammatory cytokine TGF-ß versus pro-inflammatory cytokines. In summary, the lack of this TetR-like repressor expression, within a lipid environment, may help mycobacteria overcome intracellular redox stress and survive longer inside their host. 000118916 536__ $$9info:eu-repo/grantAgreement/ES/ISCIII/PI19-00666 000118916 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/ 000118916 590__ $$a5.7$$b2022 000118916 592__ $$a1.308$$b2022 000118916 591__ $$aMICROBIOLOGY$$b28 / 135 = 0.207$$c2022$$dQ1$$eT1 000118916 593__ $$aMedicine (miscellaneous)$$c2022$$dQ1 000118916 591__ $$aIMMUNOLOGY$$b55 / 161 = 0.342$$c2022$$dQ2$$eT2 000118916 593__ $$aInfectious Diseases$$c2022$$dQ1 000118916 593__ $$aMicrobiology (medical)$$c2022$$dQ1 000118916 593__ $$aMicrobiology$$c2022$$dQ1 000118916 593__ $$aImmunology$$c2022$$dQ2 000118916 594__ $$a6.4$$b2022 000118916 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion 000118916 700__ $$aPortillo, P. del 000118916 700__ $$aAnzola, J. M. 000118916 700__ $$aAres, M. A. 000118916 700__ $$aHelguera-Repetto, A. C. 000118916 700__ $$aCerna-Cortés, J. F. 000118916 700__ $$aMéndez-Tenorio, A. 000118916 700__ $$aGarcía, M. J. 000118916 700__ $$0(orcid)0000-0003-1027-7583$$aOtal, I.$$uUniversidad de Zaragoza 000118916 700__ $$0(orcid)0000-0003-2993-5478$$aMartín, C.$$uUniversidad de Zaragoza 000118916 700__ $$aGonzalez-y-Merchand, J. A. 000118916 700__ $$aRivera-Gutiérrez, S. 000118916 7102_ $$11011$$2630$$aUniversidad de Zaragoza$$bDpto. Microb.Ped.Radio.Sal.Pú.$$cÁrea Microbiología 000118916 773__ $$g12 (2022), 907890 [19 pp.]$$tFrontiers in Cellular and Infection Microbiology$$x2235-2988 000118916 8564_ $$s5399598$$uhttps://zaguan.unizar.es/record/118916/files/texto_completo.pdf$$yVersión publicada 000118916 8564_ $$s2574742$$uhttps://zaguan.unizar.es/record/118916/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada 000118916 909CO $$ooai:zaguan.unizar.es:118916$$particulos$$pdriver 000118916 951__ $$a2024-03-18-14:49:00 000118916 980__ $$aARTICLE