title: Bacterial itaconate degradation promotes pathogenicity.
abstract: Itaconate (methylenesuccinate) was recently identified as a mammalian metabolite whose production is substantially induced during macrophage activation. This compound is a potent inhibitor of isocitrate lyase, a key enzyme of the glyoxylate cycle, which is a pathway required for the survival of many pathogens inside the eukaryotic host. Here we show that numerous bacteria, notably many pathogens such as Yersinia pestis and Pseudomonas aeruginosa, have three genes for itaconate degradation. They encode itaconate coenzyme A (CoA) transferase, itaconyl-CoA hydratase and (S)-citramalyl-CoA lyase, formerly referred to as CitE-like protein. These genes are known to be crucial for survival of some pathogens in macrophages. The corresponding enzymes convert itaconate into the cellular building blocks pyruvate and acetyl-CoA, thus enabling the bacteria to metabolize itaconate and survive in macrophages. The itaconate degradation and detoxification pathways of Yersinia and Pseudomonas are the result of convergent evolution. This work revealed a common persistence factor operating in many pathogenic bacteria.
authors.affiliation: Mikrobiologie, Fakultät Biologie, Universität Freiburg, Freiburg, Germany.
authors.forename: Jahminy
authors.initials: J
authors.lastname: Sasikaran
authors.affiliation: 1] Mikrobiologie, Fakultät Biologie, Universität Freiburg, Freiburg, Germany. [2].
authors.forename: Michał
authors.initials: M
authors.lastname: Ziemski
authors.affiliation: 1] Mikrobiologie, Fakultät Biologie, Universität Freiburg, Freiburg, Germany. [2].
authors.forename: Piotr K
authors.initials: PK
authors.lastname: Zadora
authors.affiliation: Mikrobiologie, Fakultät Biologie, Universität Freiburg, Freiburg, Germany.
authors.forename: Angela
authors.initials: A
authors.lastname: Fleig
authors.affiliation: 1] Mikrobiologie, Fakultät Biologie, Universität Freiburg, Freiburg, Germany. [2].
authors.forename: Ivan A
authors.initials: IA
authors.lastname: Berg
mesh_terms: D006801:Humans; D006868:Hydrolysis; D009876:Operon; D011550:Pseudomonas aeruginosa / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D013386:Succinates / Q000378:metabolism*; D014774:Virulence; D015010:Yersinia pestis / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*
chemical_list: D013386:Succinates; C005229:itaconic acid