OBJECTIVES The objective of this study was to determine the contribution of the CmeABC efflux pump to the emergence of fluoroquinolone (FQ)-resistant mutants in Campylobacter jejuni under various levels of selection pressure. METHODS The frequency of emergence of ciprofloxacin-resistant mutants was measured in wild-type C. jejuni NCTC 11168 and its isogenic cmeB mutant and cmeR mutant (overex...

OBJECTIVES Mutations in the gyrase genes cause fluoroquinolone resistance in Mycobacterium tuberculosis. However, the predictive value of these markers for clinical outcomes in patients with MDR-TB is unknown to date. The objective of this study was to determine molecular markers and breakpoints predicting second-line treatment outcomes in M. tuberculosis patients treated with fourth-generation...

To obtain a general framework for understanding selection of antibiotic-resistant mutants, allelic diversity was examined with about 600 fluoroquinolone-resistant mutants of mycobacteria. Selection at low fluoroquinolone concentration produced many low-level resistance mutants. Some of these contained mutations that conferred unselected antibiotic resistance; none contained alterations in the q...

Oxolinic acid (OA) resistance in field isolates of Burkholderia glumae, a causal agent of bacterial grain rot, is dependent on an amino acid substitution at position 83 in GyrA (GyrA83). In the present study, among spontaneous in vitro mutants from the OA-sensitive B. glumae strain Pg-10, we selected OA-resistant mutants that emerged at a rate of 5.7 x 10(-10). Nucleotide sequence analysis of t...

Transposon mutagenesis of a clinical isolate of Morganella morganii, G1492 (tigecycline MIC of 4 microg/ml), yielded two insertion knockout mutants for which tigecycline MICs were 0.03 microg/ml. Transposon insertions mapped to acrA, which is constitutively overexpressed in G1492, suggesting a role of the AcrAB efflux pump in decreased susceptibility to tigecycline in M. morganii.

Salmonella enterica serovar Virchow is highly prevalent in humans and farm animals in Israel. In addition to high rates of resistance to multiple antibiotics, this serovar exhibits a high incidence of resistance to nalidixic acid. More than 90% of Salmonella serovar Virchow isolates of human and poultry origin obtained from 1997 to 2004 were resistant to nalidixic acid (MIC > or = 128 microg/ml...

Two independent mutants resistant to l-arabinose inhibition only in the presence of d-glucose were isolated from an l-arabinose-sensitive strain containing the araD139 mutation. Preliminary mapping studies indicate that these mutations are closely linked to the araIOC region. Addition of d-glucose to growing cultures of these mutants results in a 95 to 98% repression of ara operon expression, a...

OBJECTIVES Besifloxacin is a new fluoroquinolone in development for ocular use. We investigated its mode of action and resistance in two major ocular pathogens, Streptococcus pneumoniae and Staphylococcus aureus, and in the reference species Escherichia coli. METHODS Primary and secondary targets of besifloxacin were evaluated by: (i) mutant selection experiments; (ii) MIC testing of defined ...

We examined the potential for the development of fluoroquinolone resistance in Neisseria meningitidis by cultivating two clinical isolates of meningococci in the presence of concentrations of ciprofloxacin at and about the predetermined MIC. The quinolone resistance determining regions (QRDRs) of gyrA and parC of 50 stable quinolone-resistant mutants derived in vitro were sequenced and compared...

We investigated the contribution of quinolone resistance-determining region (QRDR) mutations to fluoroquinolone (enrofloxacin, orbifloxacin and danofloxacin) susceptibility in 58 Mycoplasma bovis isolates from dairy cattle in Japan. Fluoroquinolone non-resistant isolates (fluoroquinolone-MICs≤2 μg/ml) possessed no QRDR mutations (19 isolates) or Ser83Leu in GyrA (32 isolates). Fluoroquinolone-r...