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Alvarez N.,Bacteriology and Mycobacteria Unit | Alvarez N.,Pontifical Bolivarian University | Zapata E.,Bacteriology and Mycobacteria Unit | Zapata E.,Pontifical Bolivarian University | And 8 more authors.
BioMed Research International | Year: 2014

We compared the prevalence of levofloxacin (LVX) resistance with that of ofloxacin (OFX) and moxifloxacin (MFX) among multidrug resistant (MDR) MTB clinical 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. © 2014 N. Alvarez et al.

PubMed | Public Health England, Research Center Borstel, University of Cambridge, German Center for Infection Research and 8 more.
Type: | Journal: Antimicrobial agents and chemotherapy | Year: 2017

We demonstrated that some non-synonymous and synonymous mutations in gyrA in Mycobacterium tuberculosis result in systematic false-resistance results to fluoroquinolones using the Hain GenoType MTBDRsl assays (version 1 and 2) by preventing the binding of wild-type probes. Moreover, such mutations can prevent the binding of mutant probes, designed for the identification of specific resistance mutations. Although these mutations are likely rare globally, they occur in approximately 7% of multidrug-resistant tuberculosis strains in some settings.

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