Work

cAMP receptor proteins in mycobacteria

Year: 2026

Type: review

Abstract: Cyclic adenosine monophosphate (cAMP) signaling is a major regulatory system in mycobacteria, and the cAMP receptor protein (CRP) serves as its principal transcriptional effector. In Mycobacterium tuberculosis, CRP controls a broad regulon associated with metabolic adaptation, respiration, cell envelope-associated processes, dormancy-related resuscitation, and virulence. Structural and biophysical studies have demonstrated that mycobacterial CRPs differ from the classical Escherichia coli paradigm: apo-CRP adopts restrained or asymmetric conformations, whereas cAMP binding promotes a more symmetric, DNA-binding-competent state and enhances the specificity of CRP-DNA interactions. In Mycobacterium smegmatis, the major paralog Crp1 (MSMEG_6189) regulates metabolic and respiratory adaptation, oxidative stress defense, and isoniazid susceptibility, whereas Crp2 (MSMEG_0539) appears to play a more limited or subsidiary role. Recent findings further reveal that CRP activity is modulated by lysine acetylation, cooperative promoter recruitment with the virulence-associated response regulator PhoP, and respiratory inhibition-induced increases in intracellular cAMP, thereby linking metabolic and respiratory status to adaptive and virulence-associated gene regulation. This review summarizes the structure, allosteric regulation, regulon, and physiological functions of mycobacterial CRPs, highlighting their role as central integrators of cAMP signaling, respiratory and metabolic state, persistence-associated physiology, and antibiotic susceptibility.

Source: The Journal of Microbiology

DOI: 10.71150/jm.2607013

Authors: Jeong-Il Oh, Yuna Oh, Yupin Hwang

Institution: Pusan National University

Language: English

Topic: Bacterial Genetics and Biotechnology

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: hybrid

Estimated APC paid: $3,690

Funder: Pusan National University