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Antibacterial Properties of the Mammalian L-Amino Acid Oxidase IL4I1.doc

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Antibacterial Properties of the Mammalian L-Amino Acid Oxidase IL4I1

AntibacterialPropertiesoftheMammalianL-AminoAcid OxidaseIL4I1 Marie-LinePuiffe1,2,IsabelleLachaise4,Vale′rieMolinier-Frenkel1,2,3*.,FlaviaCastellano 1,2,3 . * 1INSERM, U955, IMRB, Equipe 09, Cre′teil, France, 2Universite′ Paris Est, Faculte′ de Me′decine, Cre′teil, France, 3AP-HP, Ho?pital H. Mondor - A. Chenevier, Service d’ImmunologieBiologique,Cre′teil, France,4PlateformeChromatographieAnalytiqueetsemiPre′parative, ICMPE,Thiais,France Abstract L-amino acid oxidases (LAAO) are flavoproteins that catalyze the oxidative deamination of L-amino acids to a keto-acid along with the production of H2O2 and ammonia. Interleukin 4 induced gene 1 (IL4I1) is a secreted LAAO expressed by macrophages and dendritic cells stimulated by microbial derived products or interferons, which is endowed with immunoregulatoryproperties.ItisthefirstLAAOdescribedinmammalianinnateimmunecells.Inthiswork,weshowthat this enzymeblocks the invitro andinvivo growthof Gram negativeandGram positivebacteria. Thisantibiotic effect is primarily mediated by H2O2 production but is amplified by basification of the medium due to the accumulation of ammonia.Thedepletionofphenylalanine(theprimaryaminoacidcatabolizedbyIL4I1)mayalsoparticipateintheinvivo inhibitionofstaphylococcigrowth.Thus,IL4I1playsadistinctrolecomparedtootherantibacterialenzymesproducedby mononuclearphagocytes. Citation:PuiffeM-L,LachaiseI,Molinier-FrenkelV,CastellanoF(2013)AntibacterialPropertiesoftheMammalianL-AminoAcidOxidaseIL4I1.PLoSONE8(1): e54589.doi:10.1371/journal.pone.0054589 Editor:PauloLeeHo,InstitutoButantan,Brazil ReceivedMay22,2012;AcceptedDecember14,2012;PublishedJanuary23,2013 Copyright: ? 2013 Puiffe etal. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding:ThisworkwassupportedbygrantA1L9-SEfromInstitutNationaldelaSante′ etdelaRecherche