Acetylation of Cyclic AMP Receptor Protein by Acetyl Phosphate Modulates Mycobacterial Virulence

Di, Yuchang; Xu, Siyue; Chi, Mingzhe; Hu, Youwei; Zhang, Xiao; Wang, Honghai; Zhang, Wenhong; Zhang, Xuelian

doi:10.1128/spectrum.04002-22

Cited by 6 publications

(5 citation statements)

References 66 publications

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“…48 KAc of OM proteins has been associated with altered antibiotic resistance and biofilm formation, 65−68 however the mechanism remains unknown; our data provide evidence for a role in virulenceassociated phenotypes such as cell adherence and immune response. An association between KAc and virulence has been observed recently in other bacteria, 69 however this is largely due to effects at the regulatory level 70,71 or on enzyme catalysis. 72 C. jejuni recognizes in vivo signals, such as DOC, by increasing motility, antibiotic resistance, and expression of factors required for adherence to, and invasion of, human intestinal epithelial cells.…”

Section: ■ Discussionmentioning

confidence: 93%

“…KAc of OM proteins has been associated with altered antibiotic resistance and biofilm formation, − however the mechanism remains unknown; our data provide evidence for a role in virulence-associated phenotypes such as cell adherence and immune response. An association between KAc and virulence has been observed recently in other bacteria, however this is largely due to effects at the regulatory level , or on enzyme catalysis …”

Section: Discussionmentioning

confidence: 96%

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Global Acetylomics of Campylobacter jejuni Shows Lysine Acetylation Regulates CadF Adhesin Processing and Human Fibronectin Binding

Dale,

Man,

Cordwell

2023

J. Proteome Res.

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Lysine acetylation (KAc) is a reversible post-translational modification (PTM) that can alter protein structure and function; however, specific roles for KAc are largely undefined in bacteria. Acetyl-lysine immunoprecipitation and LC–MS/MS identified 5567 acetylated lysines on 1026 proteins from the gastrointestinal pathogen Campylobacter jejuni (∼63% of the predicted proteome). KAc was identified on proteins from all subcellular locations, including the outer membrane (OM) and extracellular proteins. Label-based LC–MS/MS identified proteins and KAc sites during growth in 0.1% sodium deoxycholate (DOC, a component of gut bile salts). 3410 acetylated peptides were quantified, and 784 (from 409 proteins) were differentially abundant in DOC growth. Changes in KAc involved multiple pathways, suggesting a dynamic role for this PTM in bile resistance. As observed elsewhere, we show KAc is primarily nonenzymatically mediated via acetyl-phosphate; however, the deacetylase CobB also contributes to a global elevation of this modification in DOC. We observed several multiply acetylated OM proteins and altered DOC abundance of acetylated peptides in the fibronectin (Fn)-binding adhesin CadF. We show KAc reduces CadF Fn binding and prevalence of lower mass variants. This study provides the first system-wide lysine acetylome of C. jejuni and contributes to our understanding of KAc as an emerging PTM in bacteria.

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Section: ■ Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 96%

Global Acetylomics of Campylobacter jejuni Shows Lysine Acetylation Regulates CadF Adhesin Processing and Human Fibronectin Binding

Dale,

Man,

Cordwell

2023

J. Proteome Res.

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“…Similar to E. coli CAP and V. cholera Crp, Rv3676 activity can be modulated by acetylation. This modification at the conserved lysine 193 inhibits DNA binding and transcription activation and occurs less frequently under Crp-activating conditions, such as the presence of cAMP, low pH, high temperature, or oxidative stress (Di et al 2023 ). Rv3676 acetylation can be reversed by the action of a NAD + -dependent deacetylase, providing an additional level of controlling Rv3676-mediated regulation of the bacterial pathogenicity (Di et al 2023 ).…”

Section: Actinobacteriamentioning

confidence: 99%

“…This modification at the conserved lysine 193 inhibits DNA binding and transcription activation and occurs less frequently under Crp-activating conditions, such as the presence of cAMP, low pH, high temperature, or oxidative stress (Di et al 2023 ). Rv3676 acetylation can be reversed by the action of a NAD + -dependent deacetylase, providing an additional level of controlling Rv3676-mediated regulation of the bacterial pathogenicity (Di et al 2023 ). Interestingly, in M. tuberculosis and M. smegmatis , cAMP binds to the NBD of a GCN5-related N -acetyltransferase and promotes its activity in lysine acetylation of the universal stress protein USP (Nambi et al 2010 ).…”

Section: Actinobacteriamentioning

confidence: 99%

Structural and functional diversity of bacterial cyclic nucleotide perception by CRP proteins

et al. 2023

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Cyclic AMP (cAMP) is a ubiquitous second messenger synthesized by most living organisms. In bacteria, it plays highly diverse roles in metabolism, host colonization, motility, and many other processes important for optimal fitness. The main route of cAMP perception is through transcription factors from the diverse and versatile CRP-FNR protein superfamily. Since the discovery of the very first CRP protein CAP in Escherichia coli more than four decades ago, its homologs have been characterized in both closely related and distant bacterial species. The cAMP-mediated gene activation for carbon catabolism by a CRP protein in the absence of glucose seems to be restricted to E. coli and its close relatives. In other phyla, the regulatory targets are more diverse. In addition to cAMP, cGMP has recently been identified as a ligand of certain CRP proteins. In a CRP dimer, each of the two cyclic nucleotide molecules makes contacts with both protein subunits and effectuates a conformational change that favors DNA binding. Here, we summarize the current knowledge on structural and physiological aspects of E. coli CAP compared with other cAMP- and cGMP-activated transcription factors, and point to emerging trends in metabolic regulation related to lysine modification and membrane association of CRP proteins.

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“…Studies have demonstrated that the acetylation of a conserved lysine 193 (K193) within the C-terminal DNA-binding domain of the cyclic AMP (cAMP) receptor protein (CRP) reduces its DNA-binding ability and inhibits transcriptional activity. The reversible acetylation status of CRP K193 has been shown to significantly affect mycobacterial growth phenotype, alter the stress response, and regulate the expression of biologically relevant genes ( Di et al., 2023 ). Shi SP.…”

Section: Acetylation Modification Of Proteins In M Tbmentioning

confidence: 99%

The role of Mycobacterium tuberculosis acetyltransferase and protein acetylation modifications in tuberculosis

Huang¹,

Zhu²,

Pan³

et al. 2023

Front. Cell. Infect. Microbiol.

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Tuberculosis (TB) is a widespread infectious disease caused by Mycobacterium tuberculosis (M. tb), which has been a significant burden for a long time. Post-translational modifications (PTMs) are essential for protein function in both eukaryotic and prokaryotic cells. This review focuses on the contribution of protein acetylation to the function of M. tb and its infected macrophages. The acetylation of M. tb proteins plays a critical role in virulence, drug resistance, regulation of metabolism, and host anti-TB immune response. Similarly, the PTMs of host proteins induced by M. tb are crucial for the development, treatment, and prevention of diseases. Host protein acetylation induced by M. tb is significant in regulating host immunity against TB, which substantially affects the disease’s development. The review summarizes the functions and mechanisms of M. tb acetyltransferase in virulence and drug resistance. It also discusses the role and mechanism of M. tb in regulating host protein acetylation and immune response regulation. Furthermore, the current scenario of isoniazid usage in M. tb therapy treatment is examined. Overall, this review provides valuable information that can serve as a preliminary basis for studying pathogenic research, developing new drugs, exploring in-depth drug resistance mechanisms, and providing precise treatment for TB.

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Acetylation of Cyclic AMP Receptor Protein by Acetyl Phosphate Modulates Mycobacterial Virulence

Cited by 6 publications

References 66 publications

Global Acetylomics of Campylobacter jejuni Shows Lysine Acetylation Regulates CadF Adhesin Processing and Human Fibronectin Binding

Global Acetylomics of Campylobacter jejuni Shows Lysine Acetylation Regulates CadF Adhesin Processing and Human Fibronectin Binding

Structural and functional diversity of bacterial cyclic nucleotide perception by CRP proteins

The role of Mycobacterium tuberculosis acetyltransferase and protein acetylation modifications in tuberculosis

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