03066naa a2200313 a 450000100080000000500110000800800410001902200140006002400380007410000180011224501480013026000090027850014060028752006980169365300230239165300150241465300190242965300170244865300320246570000200249770000160251770000210253370000170255470000150257170000170258670000180260370000190262177301120264010649022024-10-30 2024 bl uuuu u00u1 u #d a1932-62037 a10.1371/journal.pone.03110402DOI1 aIMELIO, J. A. aSignal-sensing triggers the shutdown of HemKR, regulating heme and iron metabolism in the spirochete Leptospira biflexa.h[electronic resource] c2024 aArticle history: Received 12 July 2024, Accepted 11 September 2024, Published 26 September 2024. -- Correspondence: Buschiazzo, A.; Laboratory of Molecular & Structural Microbiology, Institut Pasteur de Montevideo, Montevideo, Uruguay; email:alebus@pasteur.edu.uy -- Editor: Brian Stevenson, University of Kentucky College of Medicine, United States of America. -- Document type: Article, Gold Open Access. -- Publisher: Public Library of Science. -- License: This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ ). -- Funding: AB was supported by grants #FCE_1_2017_1_136291 (Agencia Nacional de Investigacion e Innovacion https://www.anii.org.uy/); and #PIU_761 Pasteur International Joint Research Unit IMiZA (Institut Pasteur/Institut Pasteur de Montevideo https://www.pasteur.fr/en/ & https://pasteur.uy/en/) MP was supported by grant #PIU_761 Pasteur International Joint Research Unit IMiZA (Institut Pasteur/Institut Pasteur de Montevideo https://www.pasteur.fr/en/ & https://pasteur.uy/en/) JAI had a PhD fellowship POS_NAC_2016_1_ 129903 (Agencia Nacional de Investigacion e Innovacion https://www.anii.org.uy/ ) TC was supported by grants #ANR-10-INBS-09 (Agence Nationale de la Recherche https://anr.fr/ en/) and IBISA (Infrastructures en Biologie, Sante et Agronomie https://www.ibisa.net/). aABSTRACT.- Heme and iron metabolic pathways are highly intertwined, both compounds being essential for key biological processes, yet becoming toxic if overabundant.Their concentrations are exquisitely regulated, including via dedicated two-component systems (TCSs) that sense signals and regulate adaptive responses.HemKR is a TCS present in both saprophytic and pathogenic Leptospira species, involved in the control of heme metabolism.However, the molecular means by which HemKR is switched on/off in a signal-dependent way, are still unknown.Moreover, a comprehensive list of HemKR-regulated genes, potentially overlapped with iron-responsive targets, is also missing. © 2024 Imelio et al. aBacterial Proteins aLeptospira aRNA extraction aRNA sequence aUNIDAD MIXTA PASTEUR + INIA1 aTRAJTENBERG, F.1 aMONDINO, S.1 aZARANTONELLI, L.1 aVITRENKO, I.1 aLEMÉE, L.1 aCOKELAER, T.1 aPICARDEAU, M.1 aBUSCHIAZZO, A. tPLoS ONE, 2024, Volume 19, Issue 9, e0311040. https://doi.org/10.1371/journal.pone.0311040 -- OPEN ACCESS.