title: AmiA is a penicillin target enzyme with dual activity in the intracellular pathogen Chlamydia pneumoniae.
abstract: Intracellular Chlamydiaceae do not need to resist osmotic challenges and a functional cell wall was not detected in these pathogens. Nevertheless, a recent study revealed evidence for circular peptidoglycan-like structures in Chlamydiaceae and penicillin inhibits cytokinesis, a phenomenon known as the chlamydial anomaly. Here, by characterizing a cell wall precursor-processing enzyme, we provide insights into the mechanisms underlying this mystery. We show that AmiA from Chlamydia pneumoniae separates daughter cells in an Escherichia coli amidase mutant. Contrary to homologues from free-living bacteria, chlamydial AmiA uses lipid II as a substrate and has dual activity, acting as an amidase and a carboxypeptidase. The latter function is penicillin sensitive and assigned to a penicillin-binding protein motif. Consistent with the lack of a regulatory domain in AmiA, chlamydial CPn0902, annotated as NlpD, is a carboxypeptidase, rather than an amidase activator, which is the case for E. coli NlpD. Functional conservation of AmiA implicates a role in cytokinesis and host response modulation.
authors: 1] Institute for Medical Microbiology, Immunology and Parasitology (IMMIP), Pharmaceutical Microbiology, University of Bonn, 53115 Bonn, Germany [2].
authors: Anna
authors: A
authors: Klöckner
authors: 1] Institute for Medical Microbiology, Immunology and Parasitology (IMMIP), Pharmaceutical Microbiology, University of Bonn, 53115 Bonn, Germany [2].
authors: Christian
authors: C
authors: Otten
authors: 1] The Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, NE2 4AX, UK [2].
authors: Adeline
authors: A
authors: Derouaux
authors: The Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, NE2 4AX, UK.
authors: Waldemar
authors: W
authors: Vollmer
authors: Institute for Medical Microbiology, Immunology and Parasitology (IMMIP), Pharmaceutical Microbiology, University of Bonn, 53115 Bonn, Germany.
authors: Henrike
authors: H
authors: Bühl
authors: Institute for Medical Microbiology, Immunology and Parasitology (IMMIP), Pharmaceutical Microbiology, University of Bonn, 53115 Bonn, Germany.
authors: Stefania
authors: S
authors: De Benedetti
authors: Institute for Medical Microbiology, Immunology and Parasitology (IMMIP), Pharmaceutical Microbiology, University of Bonn, 53115 Bonn, Germany.
authors: Daniela
authors: D
authors: Münch
authors: Institute for Medical Microbiology, Immunology and Parasitology (IMMIP), Pharmaceutical Microbiology, University of Bonn, 53115 Bonn, Germany.
authors: Michaele
authors: M
authors: Josten
authors: Institute of Functional Microbial Genomics, University of Düsseldorf, 40225 Düsseldorf, Germany.
authors: Katja
authors: K
authors: Mölleken
authors: Institute for Medical Microbiology, Immunology and Parasitology (IMMIP), Pharmaceutical Microbiology, University of Bonn, 53115 Bonn, Germany.
authors: Hans-Georg
authors: HG
authors: Sahl
authors: Institute for Medical Microbiology, Immunology and Parasitology (IMMIP), Pharmaceutical Microbiology, University of Bonn, 53115 Bonn, Germany.
authors: Beate
authors: B
authors: Henrichfreise
mesh_terms: D000581:Amidohydrolases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002268:Carboxypeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002473:Cell Wall / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D016993:Chlamydophila pneumoniae / Q000166:cytology / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D048749:Cytokinesis; D008969:Molecular Sequence Data; D010406:Penicillins / Q000494:pharmacology*; D016415:Sequence Alignment
chemical_list: D001426:Bacterial Proteins; D010406:Penicillins; D002268:Carboxypeptidases; D000581:Amidohydrolases; C019665:amidase