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Methicillin-resistant Staphylococcus aureus (MRSA) is a major hospital-acquired infective pathogen that has developed resistance to many antibiotics. It is imperious to develop novel anti-MRSA drugs to control the emergence of drug resistance. The biosynthesis of cysteine in bacteria is catalyzed by CysE and CysK. CysE was predicted to be important for bacterial viability, it could be a potential drug target. The serine acetyltransferase activity of CysE was detected and its catalytic properties were also determined. CysE homology model was built to investigate interaction sites between CysE and substrate L-Ser or inhibitors by molecular docking. Docking data showed that residues Asp94 and His95 were essential for serine acetyltransferase activity of CysE, which were confirmed by site-directed mutagenesis. Colorimetric assay was used to screen natural products and six compounds which inhibited CysE activity (IC ranging from 29.83 μM to 203.13 μM) were found. Inhibition types of two compounds 4 (11-oxo-ebracteolatanolide B) and 30 ((4R,4aR)-dihydroxy-3-hydroxymethyl-7,7,10a-trimethyl-2,4,4a,5,6,6a,7,8,9,10,10a,l0b-dodecahydrophenanthro[3,2-b]furan-2-one) on CysE were determined. Compounds 4 and 30 showed inhibitory effect on MRSA growth (MIC at 12.5 μg/ml and 25 μg/ml) and mature biofilm. The established colorimetric assay will facilitate further high-throughput screening of CysE inhibitors from different compound libraries. The compounds 4 and 30 may offer structural basis for developing new anti-MRSA drugs.
This article was published in the following journal.
Name: Microbial pathogenesis
Methicillin resistant Staphylococcus aureus (MRSA) remains an important cause of healthcare-associated infections. Here, we describe the development of methicillin-resistant isolates among nosocomial ...
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A strain of Staphylococcus aureus that is non-susceptible to the action of METHICILLIN. The mechanism of resistance usually involves modification of normal or the presence of acquired PENICILLIN BINDING PROTEINS.
A species of STAPHYLOCOCCUS similar to STAPHYLOCOCCUS HAEMOLYTICUS, but containing different esterases. The subspecies Staphylococcus hominis novobiosepticus is highly virulent and novobiocin resistant.
A COAGULASE-negative species of STAPHYLOCOCCUS found on the skin and MUCOUS MEMBRANE of warm-blooded animals. Similar to STAPHYLOCOCCUS EPIDERMIDIS and STAPHYLOCOCCUS HAEMOLYTICUS, it is a nosocomial pathogen in NICU settings. Subspecies include generally antibiotic susceptible and BIOFILM negative capitis and antibiotic resistant and biofilm positive urealyticus isolates.
An enzyme that catalyzes the conversion of L-SERINE to COENZYME A and O-acetyl-L-serine, using ACETYL-COA as a donor.
One of the PENICILLINS which is resistant to PENICILLINASE but susceptible to a penicillin-binding protein. It is inactivated by gastric acid so administered by injection.
MRSA (methicillin-resistant Staphylococcus aureus)
MRSA (methicillin-resistant Staphylococcus aureus) is a family of bacteria with resistance to one or more major antibiotics. There are currently 17 different strains of MRSA. Two particular strains, EMRSA15 and EMRSA16 account for 96% of MRSA blood...
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Pharmacy is the science and technique of preparing as well as dispensing drugs and medicines. It is a health profession that links health sciences with chemical sciences and aims to ensure the safe and effective use of pharmaceutical drugs. The scope of...