Selective trihydroxyazepane NagZ inhibitors increase sensitivity of Pseudomonas aeruginosa to β-lactams.
نویسندگان
چکیده
AmpC β-lactamase confers resistance to β-lactam antibiotics in many Gram negative bacteria. Inducible expression of AmpC requires an N-acetylglucosaminidase termed NagZ. Here we describe the synthesis and characterization of hydroxyazepane inhibitors of NagZ. We find that these inhibitors enhance the susceptibility of clinically relevant Pseudomonas aeruginosa to β-lactams.
منابع مشابه
The Development of Selective Inhibitors of NagZ: Increased Susceptibility of Gram-Negative Bacteria to β-Lactams
The increasing incidence of inducible chromosomal AmpC β-lactamases within the clinic is a growing concern because these enzymes deactivate a broad range of even the most recently developed β-lactam antibiotics. As a result, new strategies are needed to block the action of this antibiotic resistance enzyme. Presented here is a strategy to combat the action of inducible AmpC by inhibiting the β-...
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Constitutive AmpC hyperproduction is the most frequent mechanism of resistance to the weak AmpC inducers antipseudomonal penicillins and cephalosporins. Previously, we demonstrated that inhibition of the β-N-acetylglucosaminidase NagZ prevents and reverts this mechanism of resistance, which is caused by ampD and/or dacB (PBP4) mutations in Pseudomonas aeruginosa. In this work, we compared NagZ ...
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متن کاملPharmacodynamic study of β-lactams alone and in combination with β-lactamase inhibitors against Pseudomonas aeruginosa possessing an inducible β-lactamase
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متن کاملLoss of membrane‐bound lytic transglycosylases increases outer membrane permeability and β‐lactam sensitivity in Pseudomonas aeruginosa
The opportunistic pathogen Pseudomonas aeruginosa is a leading cause of nosocomial infections. Its relatively impermeable outer membrane (OM) limits antibiotic entry, and a chromosomally encoded AmpC β-lactamase inactivates β-lactam antibiotics. AmpC expression is linked to peptidoglycan (PG) recycling, and soluble (sLT) or membrane-bound (mLT) lytic transglycosylases are responsible for genera...
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عنوان ژورنال:
- Chemical communications
دوره 49 93 شماره
صفحات -
تاریخ انتشار 2013