AmiA is a penicillin target enzyme with dual activity in the intracellular pathogen Chlamydia pneumoniae
نویسندگان
چکیده
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.
منابع مشابه
Isolation of a Penicillin Acylase Producing E.coli and Kinetic Characterization of the Whole Cell Enzyme Activity
Penicillin acylase (EC 3.5.1.11) has been a target of study for a long time because of its pivotal role in the deacylation of the penicillin into the 6- aminopenicillanic acid (6-APA) and the side-chain organic acids. This property of penicillin acylase has been exploited commercially for large scale production of 6-APA, which is the key intermediate in the manufacture of semi-synthetic penicil...
متن کاملبررسی فراوانی عفونت کلامیدیا پنومونیه در نسج آدنوئید کودکان آدنوئیدکتومی شده در مجتمع حضرت رسول اکرم(ص) تهران، 85-1384
Background & Aim: Recurrent or chronic adenotonsillar infections mainly affect children. The prevalence of potential respiratory pathogens on the adenoid and tonsillar surfaces of children with moderate symptoms of recurrent tonsillopharyngitis and/or adeno tonsillar hypertrophy differs only slightly from that in children without symptoms of adenotonsillar disease. Chlamydia pneumoniae is a...
متن کاملIn vitro Antibacterial Evaluation of Newly Synthesized Heterocyclic Compounds Against Streptococcus Pneumoniae
In recent years, the spread of drug-resistant strains of Streptococcus pneumoniae, as the most common causes of bacterial respiratory infections, threatens public health. Therefore, the use of new antimicrobial medicines to inhibit this pathogen is an urgent demand. In this research project, the inhibitory effects of thirty recently synthesized compounds including thiazole, thiazolidine, imidaz...
متن کاملAmphipathic β2,2-Amino Acid Derivatives Suppress Infectivity and Disrupt the Intracellular Replication Cycle of Chlamydia pneumoniae
We demonstrate in the current work that small cationic antimicrobial β2,2-amino acid derivatives (Mw < 500 Da) are highly potent against Chlamydia pneumoniae at clinical relevant concentrations (< 5 μM, i.e. < 3.4 μg/mL). C. pneumoniae is an atypical respiratory pathogen associated with frequent treatment failures and persistent infections. This gram-negative bacterium has a biphasic life cycle...
متن کاملLead Discovery Strategies for Identification of Chlamydia pneumoniae Inhibitors
Throughout its known history, the gram-negative bacterium Chlamydia pneumoniae has remained a challenging target for antibacterial chemotherapy and drug discovery. Owing to its well-known propensity for persistence and recent reports on antimicrobial resistence within closely related species, new approaches for targeting this ubiquitous human pathogen are urgently needed. In this review, we des...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره 5 شماره
صفحات -
تاریخ انتشار 2014