The Structural Modeling of the Interaction between Levofloxacin and theMycobacterium tuberculosisGyrase Catalytic Site Sheds Light on the Mechanisms of Fluoroquinolones Resistant Tuberculosis in Colombian Clinical Isolates
| Autor: | F. Rouzaud, P. Araque, E. Zapata, Gloria Isabel Mejía, N. Alvarez, C. Peláez, Teresa Realpe, Jaime Robledo |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Male
Article Subject medicine.drug_class Mutation Missense lcsh:Medicine Levofloxacin Colombia Crystallography X-Ray medicine.disease_cause DNA gyrase General Biochemistry Genetics and Molecular Biology Microbiology Mycobacterium tuberculosis Bacterial Proteins Moxifloxacin Catalytic Domain Drug Resistance Multiple Bacterial Tuberculosis Multidrug-Resistant medicine Humans Mutation General Immunology and Microbiology biology lcsh:R General Medicine biology.organism_classification Quinolone Virology Anti-Bacterial Agents Molecular Docking Simulation Multiple drug resistance Amino Acid Substitution DNA Gyrase Female Ofloxacin Research Article medicine.drug |
| Zdroj: | BioMed Research International BioMed Research International, Vol 2014 (2014) |
| ISSN: | 2314-6141 2314-6133 |
| DOI: | 10.1155/2014/367268 |
| Popis: | We compared the prevalence of levofloxacin (LVX) resistance with that of ofloxacin (OFX) and moxifloxacin (MFX) among multidrug resistant (MDR)MTBclinical isolates collected in Medellin, Colombia, between 2004 and 2009 and aimed at unraveling the underlying molecular mechanisms that explain the correlation between QRDR-A mutations and LVX resistance phenotype. We tested 104 MDR isolates for their susceptibility to OFX, MFX, and LVX. Resistance to OFX was encountered in 10 (9.6%) of the isolates among which 8 (7.7%) were also resistant to LVX and 6 (5.7%) to MFX. Four isolates resistant to the 3 FQ were harboring the Asp94Gly substitution, whilst 2 other isolates resistant to OFX and LVX presented the Ala90Val mutation. No mutations were found in the QRDR-B region. The molecular modeling of the interaction between LVX and the DNA-DNA gyrase complex indicates that the loss of an acetyl group in the Asp94Gly mutation removes the acid base interaction with LVX necessary for the quinolone activity. The Ala90Val mutation that substitutes a methyl for an isopropyl group induces a steric modification that blocks the LVX access to the gyrase catalytic site. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|