Abstract
BackgroundThe Ada-dependent adaptive response system in Escherichia coli is important for increasing resistance to alkylation damage. However, the global transcriptional and translational changes during this response have not been reported. Here we present time-dependent global gene and protein expression profiles following treatment with methyl methanesulfonate (MMS) in E. coli W3110 and its ada mutant strains.ResultsTranscriptome profiling showed that 1138 and 2177 genes were differentially expressed in response to MMS treatment in the wild-type and mutant strains, respectively. A total of 81 protein spots representing 76 nonredundant proteins differentially expressed were identified using 2-DE and LC-MS/MS. In the wild-type strain, many genes were differentially expressed upon long-exposure to MMS, due to both adaptive responses and stationary phase responses. In the ada mutant strain, the genes involved in DNA replication, recombination, modification and repair were up-regulated 0.5 h after MMS treatment, indicating its connection to the SOS and other DNA repair systems. Interestingly, expression of the genes involved in flagellar biosynthesis, chemotaxis, and two-component regulatory systems related to drug or antibiotic resistance, was found to be controlled by Ada.ConclusionThese results show in detail the regulatory components and pathways controlling adaptive response and how the related genes including the Ada regulon are expressed with this response.
Highlights
The Ada-dependent adaptive response system in Escherichia coli is important for increasing resistance to alkylation damage
Growth profiles of E. coli W3110 and ada mutant strains under methyl methanesulfonate (MMS)-treated and -untreated conditions Growth of the ada mutant strain was reduced in LB medium without MMS addition according to culture time, and reached the final optical density at 600 nm (OD600) of 3.48, which was about 1.5fold lower than that of the wild-type (Figure 1)
This indicates that the defect in the ada gene negatively influences cell growth even under the normal condition, and especially the ada product has an important role in adaptive responses when alkylating agents are present, as has been shown previously [21]
Summary
The Ada-dependent adaptive response system in Escherichia coli is important for increasing resistance to alkylation damage. We present time-dependent global gene and protein expression profiles following treatment with methyl methanesulfonate (MMS) in E. coli W3110 and its ada mutant strains. Alkylating agents are commonly used anti-cancer drugs and remain important for the treatment of several types of cancer [3,4]. Alkylating drugs are mostly methylating agents (e.g. temozolomide and streptozotocin, an antibiotic) or chloroethylating agents (e.g. carmustine, lomustine and fotemustine) [5]. The efficacies of these drugs are strongly modulated by DNA repair process. Thorough understanding and controlling of the repair processes will allow development of new therapies by protecting normal tissues or by potentiating effects in the target tissues
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