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AmiA is a penicillin target enzyme with dual activity in the intracellular pathogen Chlamydia pneumoniae

2014; Nature Portfolio; Volume: 5; Issue: 1 Linguagem: Inglês

10.1038/ncomms5201

2041-1723

Anna Klöckner, Christian Otten, Adeline Derouaux, Waldemar Vollmer, Henrike Bühl, Stefania De Benedetti, Daniela Münch, Michaele Josten, Katja Mölleken, Hans‐Georg Sahl, Beate Henrichfreise,

Escherichia coli research studies

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. Penicillin inhibits growth of chlamydial pathogens despite their lack of a conventional peptidoglycan cell wall. Here the authors report that the chlamydial amidase, AmiA, which can rescue cell division defects of an E. coli amiAmutant, has dual activity as a penicillin sensitive, lipid II-targetting carboxypeptidase.