cAMP receptor protein (CRP)-mediated resistance/tolerance in bacteria: mechanism and utilization in biotechnology

Abstract

Cyclic AMP receptor protein (CRP) is one of the seven global regulators in Escherichia coli, which regulates the expression of over 490 genes. It contains a cAMP binding N-terminal domain and a DNA binding C-terminal domain, connected via a short hinge region. Various stress-tolerant E. coli mutants had been obtained through transcriptional engineering of CRP. This review aims to shed some light on the possible mechanism behind these CRP variants, from the change in CRP structure, transcription profile, and DNA binding affinity. The amino acid substitutions are distributed along the protein-certain mutations have shown higher frequency than others, such as T127N and D138Y. β-Galactosidase reporter gene assay revealed that CRP mutants had lower binding affinity with all three classes of CRP-dependent promoters as compared to native CRP, which probably would change cellular transcription profile. Different CRP mutants would induce different cellular transcription profile in E. coli, but there are common genes differentially expressed in these variants, including upregulated gadAB and downregulated nontransporter genes aspA and tnaA, and transporter/poringenes malE, mglB, cstA, and lamB. We believe that transcriptional engineering of CRP can provide an alternative strain engineering method for E. coli and its detailed mechanism may need further investigations.

Molecular Underpinnings of Nitrite Effect on CymA-Dependent Respiration in Shewanella oneidensis

“…As a matter of fact, despite intensive studies for decades we still know little about bacterial ability to maintain cAMP homeostasis in response to environmental and metabolic signals ( Green et al, 2014 ). Crp has been a global protein under extensive investigation in the field of global transcription machinery engineering (gTME; Geng and Jiang, 2015 ). Numerous E. coli crp mutants showing improved performance under various stressful conditions, but the predominant mechanism for the elevated resistance is attributed to altered transcriptional profile, and stresses per se do not serve as a signal to mediate activity of cAMP-Crp ( Geng and Jiang, 2015 ).…”

Comparative transcriptional profiling of tildipirosin-resistant and sensitive Haemophilus parasuis

“…However, the development of CAMP resistance permits Gram-negative bacteria to avoid being killed by both the host immune system and antibiotics 35, 36 . CAMP resistance genes including HAPS_RS07240 , HAPS_RS11325 and HAPS_RS06175 encoding relative resistance proteins exhibited upregulation of gene expression (≥twofold changes), shown in Table 3.…”

Effect of cAMP Receptor Protein Gene on Growth Characteristics and Stress Resistance of Haemophilus parasuis Serovar 5

“…cAMP receptor protein (CRP) is one of seven global regulators in Escherichia coli, which can regulate ∼490 genes (Geng and Jiang, 2015). Global regulators play a vital role in the adaption of bacteria to environmental changes during the infection process.…”

“…Global regulators play a vital role in the adaption of bacteria to environmental changes during the infection process. Previous studies have demonstrated that CRP could improve the performance of E. coli under various stressful conditions, including osmotic pressure, bioalcohol stress, oxidative stress, low pH, and in acetate and organic solvents (Zhang et al, 2012c;Basak et al, 2014;Geng and Jiang, 2015). CRP is the first prokaryotic transcription factor purified and crystallized from E. coli and also the most comprehensively characterized regulator (Emmer et al, 1970;McKay and Steitz, 1981).…”