In addition, it has been demonstrated that DNA repair is enhanced in drug-resistant cell lines and tumors [3]. These results indicate that the expression of drug or antibiotic resistance genes might be affected in the DNA repair processes. In addition,

proteome analysis indicated that RcsB responded to peptidoglycan damage and contributed to intrinsic antibiotic resistance of E. coli [27] was synthesized at high level in Lumacaftor the ada mutant strain. The finding allowed us to further examine the changes of the expression levels of drug or antibiotic resistance genes from transcriptome profiles. Hirakawa et al. [28] demonstrated that overexpression of fifteen genes, baeR, citB, cpxR, evgA, fimZ, kdpE, narLP, ompR, rcsB, rstA, torR, yedW, yehT and dcuR, which are response regulators of two-component signal transduction systems in E. coli, conferred increased single- or multidrug resistance. Interestingly, as shown in Figure 4, most of these genes, including the baeR, citB, cpxR, evgA, fimZ, ompR, rcsB, rstA and yedW genes, were up-regulated in the ada mutant strain at 0.5 h after MMS treatment. Expression of the cognate sensor gene of two-component transduction systems (baeRS, citAB, cpxAR, evgAS

and rstAB, but not yedVW) increased coordinately when it was cotranscribed with the regulator. Increased expression levels were also observed when the sensor was even in a separate operon (fimZ-ampC and ompR-envZ). However, no induction of these two-component transduction genes was observed in MMS-treated wild-type strain. These findings show that Decitabine concentration the up-regulated genes of the bacterial two-component signal transduction systems might confer MMS resistance in the absence of the ada gene, through the control of the expression of drug or antibiotic transporter genes [29, 30]. This type of response regulator-mediated drug resistance might be required for acquiring MMS toxicity resistance although the mechanism of the response is not yet clear. Furthermore, this is closely correlated with the finding that increased expression levels of the genes involved in transport

systems are seen in the 0.5 h profile of the ada mutant strain (Figure 4). The influx and efflux of solutes through the cell might also play a major role in intrinsic tolerance PAK6 of bacteria to drugs and toxic compounds as adaptive responses. Induction of DNA repair mechanisms The prevention of the mutagenic and lethal consequences of DNA damage requires the timely expression of DNA repair and protective genes, in order to maintain the integrity of the genome and viability of the cell. As pointed out before, Ada is an important transcriptional regulator in addition to having a direct role as a methyl acceptor during DNA repair. Thus, the up-regulated expression of the ada gene positively affects cell adaptation of alkylation damage by MMS in E. coli W3110 strain.