Abstract
Bacteria have a great capacity for adjusting their metabolism in response to environmental changes by linking extracellular stimuli to the regulation of genes by transcription factors. By working in a co-operative manner, transcription factors provide a rapid response to external threats, allowing the bacteria to survive. This review will focus on transcription factors MarA, SoxS and Rob in Escherichia coli, three members of the AraC family of proteins. These homologous proteins exemplify the ability to respond to multiple threats such as oxidative stress, drugs and toxic compounds, acidic pH, and host antimicrobial peptides. MarA, SoxS and Rob recognize similar DNA sequences in the promoter region of more than 40 regulatory target genes. As their regulons overlap, a finely tuned adaptive response allows E. coli to survive in the presence of different assaults in a co-ordinated manner. These regulators are well conserved amongst Enterobacteriaceae and due to their broad involvement in bacterial adaptation in the host, have recently been explored as targets to develop new anti-virulence agents. The regulators are also being examined for their roles in novel technologies such as biofuel production.
Highlights
Bacteria are found in every possible habitat on the planet and adaptation to changing external factors is essential for their survival and growth
Two regulators of the carbon metabolism, CRP and Cra, have been shown to control marRAB transcription. The activity of these transcriptional regulators (TRs) varies with glucose concentration: CRP is activated after binding to cAMP, which is synthesized in the absence of glucose [43], while Cra is inactivated upon interaction with inducers such as D-fructose-1-phosphate or D-fructose-1,6-biphosphate, both generated in the presence of glucose [44]
Oxidative stress is generated by oxidizing chemicals, antibacterial compounds including certain antibiotics, host defense mechanisms and normal metabolic processes resulting in the formation of the reactive oxygen species (ROS), superoxide, hydrogen peroxide and the hydroxyl radical
Summary
Bacteria are found in every possible habitat on the planet and adaptation to changing external factors is essential for their survival and growth. A recent study has identified a number of attractive candidates for MarA/SoxS/Rob-controlled loci found to play a role in persistence of E. coli in a mouse model of kidney infection [11] With this great ability to adapt to environmental threats, it is not surprising that bacteria become resistant to all classes of antimicrobial drugs. Two regulators of the carbon metabolism, CRP and Cra, have been shown to control marRAB transcription The activity of these TRs varies with glucose concentration: CRP (cyclic AMP [cAMP] receptor protein) is activated after binding to cAMP, which is synthesized in the absence of glucose [43], while Cra (catabolite repressor activator) is inactivated upon interaction with inducers such as D-fructose-1-phosphate or D-fructose-1,6-biphosphate, both generated in the presence of glucose [44]. These regulators have opposing effects on marRAB transcription: CRP positively regulates marRAB transcription [45], whereas Cra represses marRAB [46]
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