aeruginosa is an obligate aerobe, it probably metabolizes drugs and repairs DNA in different ways to S. Typhimurium, a facultative anaerobe. Recently,

differences in DNA repair mechanisms were shown to have effects on the acquisition of drug resistance (Morero & Arqarana, 2009). Such difference Doxorubicin nmr in mutagen susceptibility suggests that NNN and BP may be capable of inducing drug resistance in microorganisms other than P. aeruginosa. MNU consistently conferred resistance to Rif and to CPFX resistance in P. aeruginosa. We further examined the effect of MNU concentration on the induction of resistance to these antibacterial agents. MNU concentration dependently increased Rif or CPFX resistance in P. aeruginosa, and the incidence of Rif resistance was 10 times higher than CPFX resistance. While we found nine mutations in rpoB that conferred Rif resistance,

only one mutation in gyrA, ACC to ATC at codon 83, conferred CPFX resistance to most of the CPFX-resistant strains of P. aeruginosa found in the experiment. Of the Rif-resistant P. aeruginosa induced by mutagens, check details 93% had mutations in the rpoB gene. The amino acid changes induced by mutagens were the same as those found in Rif-resistant M. tuberculosis (Murphy et al., 2006), a finding which suggests that mutagens may be implicated in the emergence of Rif-resistant M. tuberculosis. As described earlier, different species of bacteria may have different susceptibility to specific mutagens; thus, NNN and BP may be capable of conferring Rif resistance on M. tuberculosis. It would likely be fruitful to investigate the incidence of Rif-resistant M. tuberculosis between nonsmokers and smokers. Among CPFX-resistant P. aeruginosa induced by mutagens, 80% had mutations at codons Dichloromethane dehalogenase 83 and 87 in the gyrA gene, mutations that involve amino acid substitutions.

These same mutations are found in almost all the CPFX-resistant P. aeruginosa isolated from patients (Mouneimne et al., 1999; Akasaka et al., 2001). In 20% of mutagen-induced CPFX-resistant P. aeruginosa, we found no mutations in the quinolone resistance-determining region of gyrA. Consequently, we analyzed the entire gyrA sequence, however, we were unable to find any other mutations here. To further investigate what might confer CPFX resistance, we analyzed the gyrB, parC and parE genes and found mutations in gyrB and parE. All the mutations found in these genes would also lead to amino acid changes. Such mutations in gyrB or parE have not, however, been reported in clinically isolated CPFX resistant P. aeruginosa. In 11% of the samples of CPFX-resistant P. aeruginosa, we were unable to determine a likely cause for the resistance. Mutations in the regulatory genes for efflux pump proteins, resulting in an increased expression, have been reported to confer CPFX resistance (Higgins et al., 2003). Accordingly, we analyzed the sequence of regulatory genes nfxB and mexR, but found no mutations.