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
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).