SELECTION OF A GYRA MUTANT OF MYCOBACTERIUM-TUBERCULOSIS RESISTANT TOFLUOROQUINOLONES DURING TREATMENT WITH OFLOXACIN

Citation
E. Cambau et al., SELECTION OF A GYRA MUTANT OF MYCOBACTERIUM-TUBERCULOSIS RESISTANT TOFLUOROQUINOLONES DURING TREATMENT WITH OFLOXACIN, The Journal of infectious diseases, 170(2), 1994, pp. 479-483
Citations number
15
Categorie Soggetti
Infectious Diseases
ISSN journal
00221899
Volume
170
Issue
2
Year of publication
1994
Pages
479 - 483
Database
ISI
SICI code
0022-1899(1994)170:2<479:SOAGMO>2.0.ZU;2-F
Abstract
A strain of Mycobacterium tuberculosis resistant to ofloxacin was sele cted in a patient with a long history of multidrug-resistant tuberculo sis eventually treated by ofloxacin combined with other second-line dr ugs. A mutation in the gyrA gene was hypothesized to be the mechanism of acquired resistance to ofloxacin in this strain. Chromosomal DNA of strains MTB1, isolated before treatment and susceptible to ofloxacin (MIC, 1 mu g/mL), and MTB2, isolated during treatment and resistant to ofloxacin (MIC, 32 mu g/mL), was amplified by polymerase chain reacti on (PCR) using two oligonucleotide primers highly homologous to DNA se quences flanking the quinolone resistance-determining region in gyrA o f mycobacteria. Comparison of the nucleotide sequences of the 150-bp f ragments obtained by PCR revealed a point mutation in MTB2 leading to the substitution of histidine for aspartic acid at a position correspo nding to residues involved in quinolone resistance in Escherichia coli (Asp87), Staphylococcus aureus (Glu88), and Campylobacter jejuni (Asp 90).